Abnormal Levels of Expression of Plasma MicroRNA-33 in Patients With Psoriasis

array:24 ["pii" => "S1578219014001097" "issn" => "15782190" "doi" => "10.1016/j.adengl.2014.04.003" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "949" "copyright" => "Elsevier España, S.L. and AEDV" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2014;105:497-503" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1994 "formatos" => array:3 [ "EPUB" => 41 "HTML" => 1437 "PDF" => 516 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001731014000234" "issn" => "00017310" "doi" => "10.1016/j.ad.2013.11.010" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "949" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2014;105:497-503" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1719 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 1215 "PDF" => 502 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original" "titulo" => "Alteraciones en los niveles de expresión del microARN-33 en plasma de pacientes con psoriasis" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "497" "paginaFinal" => "503" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Abnormal Levels of Expression of Plasma MicroRNA-33 in Patients With Psoriasis" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1095 "Ancho" => 1628 "Tamanyo" => 120357 ] ] "descripcion" => array:1 [ "es" => "Los niveles de expresión en plasma de miARN-33a y miARN-126 en cada muestra se calcularon mediante el método de 2-ΔΔCt<a class="elsevierStyleCrossRef" href="#bib0130">26</a>(Material y métodos). Los resultados se presentan mediante la mediana y el 25-75% percentil, y en escala logarítmica en base 10; en el eje vertical se indican los valores anti-logarítmicos. Para el análisis de los resultados se utilizó el test Wilcoxon Signed Rank y se comparó la mediana del grupo de los pacientes (n=11) con respecto a la mediana del grupo control (n=11). En el panel (a) la expresión de miARN-33 en el plasma de los controles fue más baja; se cuantificó miARN-33 en el plasma de 7 de los 11 controles estudiados (Resultados). Para el análisis se utilizó el software Graph-Pad Prism versión 5.01." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. García-Rodríguez, S. Arias-Santiago, J. Orgaz-Molina, C. Magro-Checa, I. Valenzuela, P. Navarro, R. Naranjo-Sintes, J. Sancho, M. Zubiaur" "autores" => array:9 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "García-Rodríguez" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Arias-Santiago" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Orgaz-Molina" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Magro-Checa" ] 4 => array:2 [ "nombre" => "I." "apellidos" => "Valenzuela" ] 5 => array:2 [ "nombre" => "P." "apellidos" => "Navarro" ] 6 => array:2 [ "nombre" => "R." "apellidos" => "Naranjo-Sintes" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Sancho" ] 8 => array:2 [ "nombre" => "M." "apellidos" => "Zubiaur" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219014001097" "doi" => "10.1016/j.adengl.2014.04.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219014001097?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731014000234?idApp=UINPBA000044" "url" => "/00017310/0000010500000005/v1_201405270041/S0001731014000234/v1_201405270041/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S157821901400122X" "issn" => "15782190" "doi" => "10.1016/j.adengl.2014.04.016" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "944" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Actas Dermosifiliogr. 2014;105:504-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2161 "formatos" => array:3 [ "EPUB" => 44 "HTML" => 1606 "PDF" => 511 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Prevalence of Psoriasis in Spain in the Age of Biologics" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "504" "paginaFinal" => "509" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prevalencia de la psoriasis en España en la era de los agentes biológicos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1493 "Ancho" => 3003 "Tamanyo" => 203229 ] ] "descripcion" => array:1 [ "en" => "Prevalence of psoriasis according to sex and age group." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Ferrándiz, J.M. Carrascosa, M. Toro" "autores" => array:3 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Ferrándiz" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Carrascosa" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Toro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731014000180" "doi" => "10.1016/j.ad.2013.12.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731014000180?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157821901400122X?idApp=UINPBA000044" "url" => "/15782190/0000010500000005/v1_201405281018/S157821901400122X/v1_201405281018/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219014001188" "issn" => "15782190" "doi" => "10.1016/j.adengl.2014.04.012" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "962" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2014;105:487-96" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1579 "formatos" => array:3 [ "EPUB" => 37 "HTML" => 1072 "PDF" => 470 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Patient Perspectives on Triggers, Adherence to Medical Recommendations, and Disease Control in Atopic Dermatitis: The DATOP Study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "487" "paginaFinal" => "496" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dermatitis atópica desde la perspectiva del paciente: desencadenantes, cumplimiento de las recomendaciones médicas y control de la enfermedad. Estudio DATOP" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1833 "Ancho" => 3320 "Tamanyo" => 264539 ] ] "descripcion" => array:1 [ "en" => "Percentage of adults in whom atopic dermatitis lesions were associated with a possible trigger, both generally in the course of their illness and specifically in relation to the current flare." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F.J. Ortiz de Frutos, A. Torrelo, R. de Lucas, M.A. González, A. Alomar, Á. Vera, S. Ros, A.M. Mora, J. Cuervo" "autores" => array:9 [ 0 => array:2 [ "nombre" => "F.J." "apellidos" => "Ortiz de Frutos" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Torrelo" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "de Lucas" ] 3 => array:2 [ "nombre" => "M.A." "apellidos" => "González" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Alomar" ] 5 => array:2 [ "nombre" => "Á." "apellidos" => "Vera" ] 6 => array:2 [ "nombre" => "S." "apellidos" => "Ros" ] 7 => array:2 [ "nombre" => "A.M." "apellidos" => "Mora" ] 8 => array:2 [ "nombre" => "J." "apellidos" => "Cuervo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731014000386" "doi" => "10.1016/j.ad.2014.01.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731014000386?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219014001188?idApp=UINPBA000044" "url" => "/15782190/0000010500000005/v1_201405281018/S1578219014001188/v1_201405281018/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Abnormal Levels of Expression of Plasma MicroRNA-33 in Patients With Psoriasis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "497" "paginaFinal" => "503" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "S. García-Rodríguez, S. Arias-Santiago, J. Orgaz-Molina, C. Magro-Checa, I. Valenzuela, P. Navarro, R. Naranjo-Sintes, J. Sancho, M. Zubiaur" "autores" => array:9 [ 0 => array:3 [ "nombre" => "S." "apellidos" => "García-Rodríguez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Arias-Santiago" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "1" "identificador" => "fn1" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Orgaz-Molina" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Magro-Checa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "I." "apellidos" => "Valenzuela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "P." "apellidos" => "Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "R." "apellidos" => "Naranjo-Sintes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "J." "apellidos" => "Sancho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 8 => array:4 [ "nombre" => "M." "apellidos" => "Zubiaur" "email" => array:1 [ 0 => "mzubiaur@ipb.csic.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN, Consejo Superior de Investigaciones Científicas (CSIC), Parque Tecnológico Ciencias de la Salud, Armilla, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Virgen de las Nieves, Granada, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Reumatología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Alteraciones en los niveles de expresión del microARN-33 en plasma de pacientes con psoriasis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1095 "Ancho" => 1628 "Tamanyo" => 117947 ] ] "descripcion" => array:1 [ "en" => "Plasma levels of miR-33a and miR-126 in each sample were calculated using the 2-ΔΔCT method<a class="elsevierStyleCrossRef" href="#bib0130">26</a> (see Materials and Methods). Results are presented as the median and interquartile range in logarithmic scale (base 10). Anti-logarithmic values are indicated in the vertical axes. The Wilcoxon signed rank test was used to compare the median of the patient group (n=11) with that of the control group (n=11). Plasma levels of miR-33 expression were lower in controls than in psoriasis patients (a). Plasma miR-33 levels were quantified in 7 of the 11 controls studied (see Results). Analyses were performed using Graph-Pad Prism software (version 5.01)." ] ] ] "textoCompleto" => "IntroductionThe pathogenesis of psoriasis, a chronic inflammatory disease of the skin and joints, involves genetic, environmental and immunological factors.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> Alterations in the expression of over 1000 genes have been described in psoriatic lesions.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> Moreover, recent studies have described a key role for small RNAs (20-25 nucleotides long) known as microRNAs (miRNAs or miRs) in controlling the gene expression of inflammatory proteins in skin affected by psoriasis.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> miRNAs have also been implicated in keratinocyte differentiation<a class="elsevierStyleCrossRef" href="#bib0030">6</a> and T-cell function in psoriasis.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>miRNAs are evolutionarily conserved (miRBase; <a id="intr0005" class="elsevierStyleInterRef" href="http://www.mirbase.org/">http://www.mirbase.org</a>) and bind to complementary sequences in the 3’ untranslated regions of the target mRNA, leading to inhibition of translation and mRNA degradation.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> miRNA binding to its mRNA target results in a reduction in the amount of protein produced.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>miRNAs can have many mRNA targets and act as regulators of gene expression to maintain the homeostasis of many cellular processes. miRNAs are one of the most abundant and important classes of gene regulatory molecules and constitute an additional level of regulation of gene expression.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Recent studies have demonstrated the presence of miRNAs in circulating blood.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> While the cellular origin of these circulating miRNAs is unclear, it is proposed that they are derived in part from cells of the cardiovascular system.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The alterations observed in plasma miRNA levels in response to physiological and pathological changes<a class="elsevierStyleCrossRef" href="#bib0060">12</a> have led to increased interest in the potential of miRNAs as biomarkers<a class="elsevierStyleCrossRef" href="#bib0050">10</a> and/or therapeutic targets.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Altered miRNA expression has also been described in chronic inflammatory autoimmune diseases.<a class="elsevierStyleCrossRefs" href="#bib0070">14–16</a>A recent study of psoriasis patients described alterations in the levels of circulating miRNAs and found that inhibition of tumor necrosis factor with etanercept decreased the expression levels of miRNAs implicated in inflammation and autoimmunity.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>Recent studies have identified circulating miRNAs that are involved in the posttranscriptional regulation of lipid metabolism genes<a class="elsevierStyleCrossRef" href="#bib0090">18</a>; these miRNAs include miR-33, which is implicated in the posttranscriptional regulation of cholesterol metabolism genes.<a class="elsevierStyleCrossRefs" href="#bib0090">18,19</a> miR-33 also targets genes involved in sterol transport, the metabolism of high-density lipoproteins (HDL), fatty acid oxidation, and glucose metabolism.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> In vivo silencing of miR-33results in an increase in HDL levels and promotes reverse cholesterol transport.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> There is considerable research interest in the potential of miR-33 as a novel therapeutic target in atherosclerosis and other metabolic diseases.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Circulating miRNAs identified in cardiovascular diseases<a class="elsevierStyleCrossRef" href="#bib0100">20</a> include miR-126, which participates in the posttranscriptional regulation of genes that regulate vascular function and angiogenesis.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Research suggests that patients with psoriasis have an increased incidence of cardiovascular risk factors, including metabolic syndrome, obesity, dyslipidemia, diabetes, and hypertension.<a class="elsevierStyleCrossRefs" href="#bib0110">22,23</a> Moreover, important similarities between the inflammatory mechanisms of atherosclerosis and psoriasis have been described.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> The aim of our exploratory study was to measure plasma levels of miR-33 and miR-126 in patients with plaque psoriasis. We then investigated the relationship between the expression of these miRNAs and other clinical parameters.Materials and MethodsPatients and controlsWe studied 11 adult patients with a clinical diagnosis of plaque psoriasis who had attended our hospital's dermatology department. All patients were consecutively enrolled in the study and gave their written informed consent. Seven patients had never received systemic therapy and the other 4 had not received systemic treatment in the preceding 4 to 6 weeks. Samples were collected and tested between February and May 2012. During the same period a control group of 11 healthy volunteers matched for age and sex was selected and underwent the same tests. The exclusion criteria for patients and controls included the presence of cutaneous lymphoma or other cancers and established cardiovascular disease (heart attack or stroke).Clinical and laboratory parametersThe severity of psoriasis was assessed using the Psoriasis Area Severity Index (PASI) and the involved body surface area (BSA). The weight, height, and waist circumference of patients and controls were measured and used to calculate body mass index (BMI, kg/m2). Patients with a BMI > 25 were considered overweight. Systolic and diastolic blood pressures were measured after 10 minutes on 3 occasions, and the average value was calculated. In addition, serum levels of HDL-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, C-reactive protein (CRP), and fibrinogen were measured and the erythrocyte sedimentation rate (ESR) determined in both patients and controls. The criteria of the National Cholesterol Education Program's Adult Treatment Panel III (ATP-III) report were used to assess the prevalence of metabolic syndrome.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Participants were considered to have metabolic syndrome if they fulfilled 3 or more of the following criteria: waist circumference>102cm in men and>88cm in women; ESR>10mm/h; hypertriglyceridemia>150mg/dL; HDL-C<40mg/dL in men and<50mg/dL in women; blood pressure>130/85mmHg; fasting glucose>110mg/dL.Blood and plasma samplesBlood samples were collected following standard procedures (using K2-EDTA tubes and the BD Vacutainer system; BD Diagnostics) in the hospital's laboratory. Plasma was isolated by Ficoll gradient centrifugation as previously described<a class="elsevierStyleCrossRef" href="#bib0010">2</a> and plasma aliquots were stored at -80°C until analysis.miRNA extraction and quantitative real-time polymerase chain reactionTotal RNA was isolated from 200μL of plasma from patients (n=11) and controls (n=11) supplemented with 3.5μL of 1.6 ×108 copies/μL of miRNeasy Control Serum/Plasma Spike-In (Qiagen, Catalog No. 219610), using the Qiagen miRNeasy Mini Kit (Catalog No. 21704) in accordance with the manufacturer's instructions. The quality and amount of total RNA was determined using the Experion Automated Electrophoresis System (Bio-Rad) and the NanoDrop system (Thermo Fisher), respectively. cDNA was synthesized from 1μg of total RNA using the miScript II Reverse Transcription Kit (Qiagen) following the manufacturer's recommendations. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on a CFX96 thermal cycler (Bio-Rad). Every 10μL of PCR reaction mixture contained 1X QuantiTec SYBR Green PCR Master Mix, 1X miScript Universal Primer, 1X miRNA-specific primer, and 10ng cDNA. miRNA-specific primers from Qiagen were used (Homo sapiens miR-33a, Catalog no. MS00003304; and Homo sapiens miR-126-1, Catalog No. MS00003430). The following PCR program was used: 15minutes of incubation at 95¿C (to activate the Hot Start Taq DNA polymerase) followed by 40 cycles of 15seconds at 94¿C, 30seconds at 55¿C, and 30seconds at 70¿C. The fluorescence emitted by SybrGreen was measured at the end of the extension step of each cycle. The specificity of PCR amplification was determined by performing melt curve analysis of the amplicon once the PCR was completed. This involved heating from 55¿C to 90¿C in increments of 0.5¿C every 10seconds. Quantification was performed based on the results of 3 PCR reactions per sample from each participant in the control and patient groups. The threshold cycle (Ct) was calculated using the qRT-PCR software, and was defined as the point at which the amount of amplicon detected began to increase exponentially. The results were normalized internally to the levels of miRNeasy Serum/Plasma Spike-In Control Ce-miR-39_1 (Qiagen primer, Catalog No. MS00019789). Relative transcript levels in each sample were calculated using the 2-ΔΔCT method.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>UltrasonographyPatients (n=11) and controls (n=9) underwent color Doppler ultrasonography (Acuson Antares, Siemens) of the supra-aortic trunks using a 10-5MHz transducer to detect atheromatous plaques, as previously described.<a class="elsevierStyleCrossRefs" href="#bib0010">2,23</a> A carotid intima-media thickness (IMT)>1.5cm was considered indicative of the presence of a plaque.StatisticsResults are expressed as the median and interquartile range (IQR) unless otherwise specified. Plasma expression levels of miRNAs were analyzed using the nonparametric Wilcoxon signed rank test to compare the median of the patient group with that of the control group. Where indicated, the Mann-Whitney test was used to analyze differences between patients and controls. The Fischer test was used for the analysis of qualitative variables and the Spearman test to calculate correlations Differences were considered statistically significant at P<.05 (GraphPad Prism version 5.01, GraphPad Software Inc.).EthicsThe study protocol was approved by the research and ethics committees of the hospital and research institute.ResultsClinical dataThe patient and control groups both consisted of 5 males and 6 females. While the median age was somewhat higher in the patient group, this difference was not statistically significant (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). All participants were white. In the patient group the median disease activity scores (PASI and BSA) were>10 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and the median duration of disease was 5 years.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The median IMT in patients was 0.57mm (IQR, 0.54-0.61), as compared with 0.50mm in controls (IQR, 0.48-0.54) (P=.0055). One of the patients presented carotid atherosclerotic plaques.We observed no significant differences between patients and controls in levels of HDL-C, LDL-C, triglycerides, glucose, or insulin (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). One of the patients had metabolic syndrome according to ATP-III criteria.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Positive correlations were detected between triglyceride levels and plasma levels of glucose (r=0.7900, P=.0038, n=11), insulin (r=0.8018, P=.0030, n=11), and fibrinogen (r=0.6651, P=.0255, n=11). LDL-C levels were correlated with disease duration (r=0.8219, P=.0019, n=11), and HDL-C levels were inversely correlated with PASI score (r=-0.6391, P=.0343, n=11), BMI (r=-0.6273, P=.0388, n=11), and systolic blood pressure (r=-0.6651, P=.0255, n=11). Analysis of obesity parameters revealed no differences in BMI, ESR, or waist circumference between patients and controls (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In the patient group we observed a correlation between BMI values and waist circumference (r=0.9091, P=.0001), glucose levels, (r=0.6895, P=.0189), and insulin levels (r=0.7973, P=.0033). Levels of the inflammatory marker and coagulation protein fibrinogen were higher in patients vs controls (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Increased plasma levels of miR-33 in psoriasis patientsWe observed a significant increase in the relative plasma expression levels of miR-33 in psoriasis patients (5.34; IQR, 3.12-7.96) with respect to controls (2.33; IQR, 1.71-2.84) (P=.0049, Wilcoxon signed rank test). Plasma levels of miR-33 in 4 of the controls were too low to be correctly quantified, and were thus quantified in only 7 of the 11 controls (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) A positive correlation between plasma levels of miR-33 and insulin was observed in the patient group (r=0.7289, P=.0109) but not in the control group (r = 0.1071, P = .8397, n = 7). We detected no correlation in either group between plasma miR-33 expression and clinical parameters such as weight or BMI. Insulin resistance (IR) was calculated by homeostasis model assessment (HOMA) using the following equation: HOMA-IR = [insulin×glucose]/22.5, with insulin expressed in μU/mL and glucose in mmol/L. No differences in HOMA-IR were observed between patients (1.5; IQR, 1.3-3.4) and controls (1.5; IQR, 1.2-2.02) (P = .4307, Mann-Whitney test). A positive correlation between plasma miRNA levels and HOMA-IR was observed in patients (r=0.6545, P=.0289) but not in controls (r=-0.2143, P=.6445).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>We observed no significant increase in the relative expression levels of miR-126 in the plasma of patients (0.5384; IQR, 0.2839-1.052) vs controls (0.361; IQR, 0.2806-0.5371]) (P=.0830).A negative correlation between levels of circulating miR-126 and IMT values was observed in patients (r =-0.6181, P=.0426) but not in controls (r=-0.3333, P=.3807).Finally, in the group of psoriasis patients we observed no significant correlations between plasma expression levels of miR-33 or miR-126 and the other clinical parameters analyzed.DiscussionThe main finding of this study is that plasma levels of miR-33, which is implicated in the posttranscriptional regulation of genes involved in cholesterol and glucose metabolism,<a class="elsevierStyleCrossRefs" href="#bib0090">18,19</a> are increased in patients with plaque psoriasis as compared with healthy controls and are positively correlated with plasma insulin levels and the HOMA-IR index value.There is currently growing interest in the study of circulating miRNAs given their potential as biomarkers.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Moreover, circulating miRNAs may play a key role in intercellular communication,<a class="elsevierStyleCrossRef" href="#bib0135">27</a> although this remains to be clarified. miR-33a and miR-33b are encoded in the introns of the genes that encode sterol-regulatory element-binding protein 2 (SREBP-2), a transcription factor that binds to the sterol regulatory element.<a class="elsevierStyleCrossRefs" href="#bib0090">18,19</a> It has been reported that miR-33 plays a role in the posttranscriptional suppression of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1),<a class="elsevierStyleCrossRef" href="#bib0090">18</a> leading to abnormal regulation of cholesterol efflux from macrophages. Moreover, manipulation of miR-33 levels may result in alterations in circulating HDL-C levels.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Similar results have been reported in mice lacking miR-33, suggesting that blockade of this miRNA may help to prevent atherosclerosis.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> miRNAs are gene regulatory molecules that target multiple mRNAs and regulate numerous cellular processes. In hyperinsulinemia, increases in the expression of SREBP transcription factors and miR-33 may contribute to increases and decreases in plasma levels of triglycerides and HDL-C, respectively, alterations that are included in the criteria for metabolic syndrome.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Other described targets of miR-33 include genes involved in fatty acid oxidation and glucose metabolism<a class="elsevierStyleCrossRef" href="#bib0090">18</a>; these include genes encoding insulin receptor substrate 2 and sirtuin 6 (SIRT6)—a nicotinamide adenine dinucleotide-dependent histone deacetylase implicated in molecular pathways involved in aging, inflammation, and cancer.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> miR-33 also targets genes involved in the cell cycle, cell proliferation, and inflammation.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Moreover, expression levels of miR-33 are inversely correlated with disease stage in bladder cancer patients, in whom miR-33 targets transforming growth factor β (TGF-β) signaling pathways.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>AngiomiRs, including miR-126, are miRNAs found in plasma, serum, and circulating microvescicles that play key regulatory roles in vascular development and angiogenesis.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Patients with coronary artery disease or diabetes show reduced levels of circulating miR-126 as compared with healthy controls.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Moreover, treatment with etanercept decreases miR-126 expression in the serum of patients with psoriasis.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> However, in our study we found no significant differences in miR-126 levels between psoriasis patients and healthy controls, although we did observe an inverse correlation between miR-126 expression and carotid IMT. Only 1 of the psoriasis patients had atheromatous plaques and fulfilled the criteria for metabolic syndrome.We have presented significant findings that suggest an important biological role of miR-33 in psoriasis. However, the main limitation of our study is the small size of the sample.In conclusion, analysis of the expression of circulating miRNAs such as miR-33 in the plasma of psoriasis patients can contribute to a better understanding of the mechanisms underlying the systemic inflammatory alterations experienced by these patients.Ethical DisclosuresProtection of persons and animalsThe authors declare that no experiments were performed on humans or animals during the course of this study.Data confidentialityThe authors declare that they have followed the protocols of their place of work concerning the publication of patient data and that all patients included in this study were appropriately informed and gave their written informed consent.Right to privacy and informed consentThe authors declare that no private patient data appear in this article.FundingFunding was received from the European Social Fund (European Commission-European Regional Development Fund [ERDF/FEDER]); CSIC-PI 200820I216 (to M.Z.); Junta de Andalucía (to J.A.); the Department of Innovation, Science, and Enterprise and the Department of Science and Education (CVI 226 and PC08-CTS-04 046 to J.S. and M.Z.); ME-MICINN (SAF-2008-03685) (to J.S. and M.Z.); SAF-2011-27261 (to J.S.); JAE-Doc CSIC-FEDER (postdoctoral contract to S.G.R.); and the Ministry for Equality, Health and Social Policy of the Junta de Andalusia.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "xres342711" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction and objectives" 2 => "Material and methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec324326" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres342710" "titulo" => array:5 [ 0 => "Resumen" 1 => "Introducción y objetivos" 2 => "Material y métodos" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec324327" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients and controls" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical and laboratory parameters" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Blood and plasma samples" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "miRNA extraction and quantitative real-time polymerase chain reaction" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Ultrasonography" ] 5 => array:3 [ "identificador" => "sec0040" "titulo" => "Statistics" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Ethics" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0050" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Clinical data" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Increased plasma levels of miR-33 in psoriasis patients" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0070" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Protection of persons and animals" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0090" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-06-13" "fechaAceptado" => "2013-11-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec324326" "palabras" => array:5 [ 0 => "miRNA-33" 1 => "miRNA-126" 2 => "Psoriasis" 3 => "Carotid intima-media thickness" 4 => "Insulin" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec324327" "palabras" => array:5 [ 0 => "miARN-33" 1 => "miARN-126" 2 => "Psoriasis" 3 => "Media del grosor de la íntima carotídea" 4 => "Insulina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Introduction and objectivesCirculating microRNAs (miRNA) are involved in the posttranscriptional regulation of genes associated with lipid metabolism (miRNA-33) and vascular function and angiogenesis (miRNA-126). The objective of this exploratory study was to measure plasma levels of miRNA-33 and miRNA-126 in patients with plaque psoriasis and evaluate their association with clinical parameters. Material and methodsWe studied 11 patients with plaque psoriasis. The median Psoriasis Area Severity Index (PASI) was 13 (interquartile range [IQR], 9-14) and body surface area involvement was 12 (IQR, 11-15). Eleven healthy controls matched for age and sex were also included. We analyzed cardiovascular risk factors and subclinical carotid atheromatosis. Plasma miRNAs were evaluated using quantitative real-time polymerase chain reaction. ResultsCarotid intima-media thickness was greater in patients (.57mm; IQR, .54-.61; n=11) than in controls (.50mm; IQR, .48-.54; data available for 9 controls) (P=.0055, Mann-Whitney). Expression of miRNA-33 in patients (5.34; IQR, 3.12-7.96; n=11) was significantly higher than in controls (2.33; IRQ, 1.71-2.84; only detected in 7 of 11 controls) (P=.0049, Wilcoxon signed rank). No differences in miRNA-126 levels were observed between patients and controls. In patients (n=11), we observed a positive correlation between miRNA-33 and insulin levels (r=.7289, P=.0109) and a negative correlation between miRNA-126 and carotid intima-media thickness (r=–.6181, P=.0426). ConclusionIn psoriasis patients plasma levels of lipid and glucose metabolism-related miRNA-33 are increased and correlated with insulin. The study of circulating miRNA-33 in psoriasis may provide new insights about the associated systemic inflammatory abnormalities." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Introducción y objetivosSe han identificado microARN (miARN) circulantes implicados en la regulación postranscripcional de genes del metabolismo de lípidos (miARN-33) y de la función vascular y angiogénesis (miARN-126). El objetivo de este estudio exploratorio ha sido evaluar los niveles plasmáticos de miARN-33 y miARN-126 en pacientes con psoriasis en placas y su relación con parámetros clínicos. Material y métodosSe estudiaron once pacientes con psoriasis en placas (PASI [mediana] [25-75% percentil] 13 [9-14] y BSA 12 [11-15]) y un grupo pareado en edad y sexo de 11 controles sanos. Se analizaron factores de riesgo cardiovascular y la ateromatosis carotídea subclínica. Los miARN plasmáticos se evaluaron mediante la reacción en cadena de la polimerasa cuantitativa a tiempo real (qRT-PCR). ResultadosLa media del grosor de la íntima carotídea (GIM) estaba aumentada en pacientes (0,57mm [0,54-0,61], n=11) respecto a controles (0,50mm [0,48-0,54], datos disponibles n=9) (test Mann-Whitney, p=0,0055). La expresión de miARN-33 en pacientes (5,34 [3,12–7,96], n=11) estaba significativamente aumentada respecto a controles (2,33 [1,71-2,84], n=7; solo se pudo detectar en 7 de 11) (test de Wilcoxon signed Rank, p=0,0049). No se observaron diferencias en los niveles de miARN-126 entre pacientes y controles. En pacientes se observó una correlación positiva entre miARN-33 e insulina (r=0,7289, p=0,0109, n=11); y una correlación negativa entre miARN-126 y GIM (r=–0,6181, p=0,0426, n=11). ConclusiónLos pacientes con psoriasis presentaban niveles plasmáticos aumentados de miARN-33 (metabolismo de lípidos y glucosa), que se correlacionaban con los niveles de insulina. La valoración de miARN-33 circulante puede contribuir al conocimiento de las alteraciones inflamatorias sistémicas en psoriasis." ] ] "NotaPie" => array:2 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "The two authors contributed equally." "identificador" => "fn1" ] 1 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: García-Rodríguez S, Arias-Santiago S, Orgaz-Molina J, Magro-Checa C, Valenzuela I, Navarro P, et al. Alteraciones en los niveles de expresión del microARN-33 en plasma de pacientes con psoriasis 2014;105:497–503." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1095 "Ancho" => 1628 "Tamanyo" => 117947 ] ] "descripcion" => array:1 [ "en" => "Plasma levels of miR-33a and miR-126 in each sample were calculated using the 2-ΔΔCT method<a class="elsevierStyleCrossRef" href="#bib0130">26</a> (see Materials and Methods). Results are presented as the median and interquartile range in logarithmic scale (base 10). Anti-logarithmic values are indicated in the vertical axes. The Wilcoxon signed rank test was used to compare the median of the patient group (n=11) with that of the control group (n=11). Plasma levels of miR-33 expression were lower in controls than in psoriasis patients (a). Plasma miR-33 levels were quantified in 7 of the 11 controls studied (see Results). Analyses were performed using Graph-Pad Prism software (version 5.01)." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Abbreviations: ESR, erythrocyte sedimentation rate; HDL-C, high-density lipoprotein cholesterol; IMT, intima-media thickness; LDL-C, low-density lipoprotein cholesterol." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Psoriasis Patients (Ps)(n=11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Controls (C)(n=11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">P<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (Ps vs C) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female/Male<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (55)/5 (45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (55)/5 (45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (y) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (25-42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (26-42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6924 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease duration (y) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (1-18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PASI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (9-14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BSA (maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (11-15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Carotid IMT (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.57 (0.54-0.61) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.50 (0.48-0.54)<a class="elsevierStyleCrossRef" href="#tblfn0020">d</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0055 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESR (mm/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (6-11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (5-7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0743 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C-reactive protein (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.1 (0.17-2.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.21 (0.05-1.78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.1579 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Body mass index (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.33 (23.8-31.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.53 (20.49–26.72)<a class="elsevierStyleCrossRef" href="#tblfn0025">e</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0620 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Waist circumference (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male88 (80.3-109.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male92 (92-98) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.5556 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female99.8 (84.3-108.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female81.5 (76-94.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0777 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum triglyceride levels (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 (54-112) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106 (77-150) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.2643 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDL-C (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male49 (41.5-72.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male51 (41-63.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female57 (46.8-114.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female74 (66-83.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4848 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL-C(mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">133 (67-160) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">127 (114-154) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.7676 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucose (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84 (78-103) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 (62-88) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.1577 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Insulin (μU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3 (7-13.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.2 (7.1-10.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8954 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systolic blood pressure (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120 (107-126) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">123 (114-131)<a class="elsevierStyleCrossRef" href="#tblfn0025">e</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.3783 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diastolic blood pressure(mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (66-82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (70 to 86.3)<a class="elsevierStyleCrossRef" href="#tblfn0025">e</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4579 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fibrinogen (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">389 (375-456) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">304 (243-345)<a class="elsevierStyleCrossRef" href="#tblfn0020">d</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0055 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab508515.png" ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Data are presented as the median and interquartile range, except where otherwise indicated." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Mann-Whitney test for comparative analysis between the control and psoriasis patient groups." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "Number of controls and psoriasis patients studied. Data in parentheses are percentages." ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "Data available for only 9 of the 11 controls." ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "e" "nota" => "Data available for only 10 of the 11 controls." ] ] ] "descripcion" => array:1 [ "en" => "Clinical Data<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.O. Nestle" 1 => "D.H. Kaplan" 2 => "J. 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Original Article

Abnormal Levels of Expression of Plasma MicroRNA-33 in Patients With Psoriasis

Alteraciones en los niveles de expresión del microARN-33 en plasma de pacientes con psoriasis

S. García-Rodrígueza,1, S. Arias-Santiagob,c,1, J. Orgaz-Molinab, C. Magro-Checad, I. Valenzuelac, P. Navarroa, R. Naranjo-Sintesb, J. Sanchoa, M. Zubiaura,

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mzubiaur@ipb.csic.es

Corresponding author.

a Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN, Consejo Superior de Investigaciones Científicas (CSIC), Parque Tecnológico Ciencias de la Salud, Armilla, Granada, Spain

b Departamento de Dermatología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain

c Departamento de Dermatología, Hospital Virgen de las Nieves, Granada, Spain

d Departamento de Reumatología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain

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        "titulo" => "Alteraciones en los niveles de expresi&#243;n del microARN-33 en plasma de pacientes con psoriasis"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of miR-33a and miR-126 in each sample were calculated using the 2-<span class="elsevierStyleSup">&#916;&#916;</span>CT method<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> &#40;see Materials and Methods&#41;&#46; Results are presented as the median and interquartile range in logarithmic scale &#40;base 10&#41;&#46; Anti-logarithmic values are indicated in the vertical axes&#46; The Wilcoxon signed rank test was used to compare the median of the patient group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; with that of the control group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46; Plasma levels of miR-33 expression were lower in controls than in psoriasis patients &#40;a&#41;&#46; Plasma miR-33 levels were quantified in 7 of the 11 controls studied &#40;see Results&#41;&#46; Analyses were performed using Graph-Pad Prism software &#40;version 5&#46;01&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The pathogenesis of psoriasis&#44; a chronic inflammatory disease of the skin and joints&#44; involves genetic&#44; environmental and immunological factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Alterations in the expression of over 1000 genes have been described in psoriatic lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Moreover&#44; recent studies have described a key role for small RNAs &#40;20-25 nucleotides long&#41; known as microRNAs &#40;miRNAs or miRs&#41; in controlling the gene expression of inflammatory proteins in skin affected by psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> miRNAs have also been implicated in keratinocyte differentiation<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and T-cell function in psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">miRNAs are evolutionarily conserved &#40;miRBase&#59; <a id="intr0005" class="elsevierStyleInterRef" href="http://www.mirbase.org/">http&#58;&#47;&#47;www&#46;mirbase&#46;org</a>&#41; and bind to complementary sequences in the 3&#8217; untranslated regions of the target mRNA&#44; leading to inhibition of translation and mRNA degradation&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> miRNA binding to its mRNA target results in a reduction in the amount of protein produced&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>miRNAs can have many mRNA targets and act as regulators of gene expression to maintain the homeostasis of many cellular processes&#46; miRNAs are one of the most abundant and important classes of gene regulatory molecules and constitute an additional level of regulation of gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Recent studies have demonstrated the presence of miRNAs in circulating blood&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> While the cellular origin of these circulating miRNAs is unclear&#44; it is proposed that they are derived in part from cells of the cardiovascular system&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The alterations observed in plasma miRNA levels in response to physiological and pathological changes<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> have led to increased interest in the potential of miRNAs as biomarkers<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and&#47;or therapeutic targets&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Altered miRNA expression has also been described in chronic inflammatory autoimmune diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;16</span></a>A recent study of psoriasis patients described alterations in the levels of circulating miRNAs and found that inhibition of tumor necrosis factor with etanercept decreased the expression levels of miRNAs implicated in inflammation and autoimmunity&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Recent studies have identified circulating miRNAs that are involved in the posttranscriptional regulation of lipid metabolism genes<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#59; these miRNAs include miR-33&#44; which is implicated in the posttranscriptional regulation of cholesterol metabolism genes&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> miR-33 also targets genes involved in sterol transport&#44; the metabolism of high-density lipoproteins &#40;HDL&#41;&#44; fatty acid oxidation&#44; and glucose metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In vivo silencing of miR-33<span class="elsevierStyleHsp" style=""></span>results in an increase in HDL levels and promotes reverse cholesterol transport&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> There is considerable research interest in the potential of miR-33 as a novel therapeutic target in atherosclerosis and other metabolic diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Circulating miRNAs identified in cardiovascular diseases<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> include miR-126&#44; which participates in the posttranscriptional regulation of genes that regulate vascular function and angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Research suggests that patients with psoriasis have an increased incidence of cardiovascular risk factors&#44; including metabolic syndrome&#44; obesity&#44; dyslipidemia&#44; diabetes&#44; and hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> Moreover&#44; important similarities between the inflammatory mechanisms of atherosclerosis and psoriasis have been described&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The aim of our exploratory study was to measure plasma levels of miR-33 and miR-126 in patients with plaque psoriasis&#46; We then investigated the relationship between the expression of these miRNAs and other clinical parameters&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and controls</span><p id="par0025" class="elsevierStylePara elsevierViewall">We studied 11 adult patients with a clinical diagnosis of plaque psoriasis who had attended our hospital&#39;s dermatology department&#46; All patients were consecutively enrolled in the study and gave their written informed consent&#46; Seven patients had never received systemic therapy and the other 4 had not received systemic treatment in the preceding 4 to 6 weeks&#46; Samples were collected and tested between February and May 2012&#46; During the same period a control group of 11 healthy volunteers matched for age and sex was selected and underwent the same tests&#46; The exclusion criteria for patients and controls included the presence of cutaneous lymphoma or other cancers and established cardiovascular disease &#40;heart attack or stroke&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical and laboratory parameters</span><p id="par0030" class="elsevierStylePara elsevierViewall">The severity of psoriasis was assessed using the Psoriasis Area Severity Index &#40;PASI&#41; and the involved body surface area &#40;BSA&#41;&#46; The weight&#44; height&#44; and waist circumference of patients and controls were measured and used to calculate body mass index &#40;BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; Patients with a BMI &#62; 25 were considered overweight&#46; Systolic and diastolic blood pressures were measured after 10 minutes on 3 occasions&#44; and the average value was calculated&#46; In addition&#44; serum levels of HDL-cholesterol &#40;HDL-C&#41;&#44; low-density lipoprotein cholesterol &#40;LDL-C&#41;&#44; triglycerides&#44; glucose&#44; insulin&#44; C-reactive protein &#40;CRP&#41;&#44; and fibrinogen were measured and the erythrocyte sedimentation rate &#40;ESR&#41; determined in both patients and controls&#46; The criteria of the National Cholesterol Education Program&#39;s Adult Treatment Panel III &#40;ATP-III&#41; report were used to assess the prevalence of metabolic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Participants were considered to have metabolic syndrome if they fulfilled 3 or more of the following criteria&#58; waist circumference<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>102<span class="elsevierStyleHsp" style=""></span>cm in men and<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>88<span class="elsevierStyleHsp" style=""></span>cm in women&#59; ESR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#59; hypertriglyceridemia<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; HDL-C<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in men and<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in women&#59; blood pressure<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>130&#47;85<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>Hg&#59; fasting glucose<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>110<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Blood and plasma samples</span><p id="par0035" class="elsevierStylePara elsevierViewall">Blood samples were collected following standard procedures &#40;using K<span class="elsevierStyleInf">2</span>-EDTA tubes and the BD Vacutainer system&#59; BD Diagnostics&#41; in the hospital&#39;s laboratory&#46; Plasma was isolated by Ficoll gradient centrifugation as previously described<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and plasma aliquots were stored at -80&#176;C until analysis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">miRNA extraction and quantitative real-time polymerase chain reaction</span><p id="par0040" class="elsevierStylePara elsevierViewall">Total RNA was isolated from 200<span class="elsevierStyleHsp" style=""></span>&#956;L of plasma from patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; and controls &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; supplemented with 3&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;L of 1&#46;6 <span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">8</span> copies&#47;&#956;L of miRNeasy Control Serum&#47;Plasma Spike-In &#40;Qiagen&#44; Catalog No&#46; 219610&#41;&#44; using the Qiagen miRNeasy Mini Kit &#40;Catalog No&#46; 21704&#41; in accordance with the manufacturer&#39;s instructions&#46; The quality and amount of total RNA was determined using the Experion Automated Electrophoresis System &#40;Bio-Rad&#41; and the NanoDrop system &#40;Thermo Fisher&#41;&#44; respectively&#46; cDNA was synthesized from 1<span class="elsevierStyleHsp" style=""></span>&#956;g of total RNA using the miScript II Reverse Transcription Kit &#40;Qiagen&#41; following the manufacturer&#39;s recommendations&#46; Quantitative real-time polymerase chain reaction &#40;qRT-PCR&#41; was performed on a CFX96 thermal cycler &#40;Bio-Rad&#41;&#46; Every 10<span class="elsevierStyleHsp" style=""></span>&#956;L of PCR reaction mixture contained 1X QuantiTec SYBR Green PCR Master Mix&#44; 1X miScript Universal Primer&#44; 1X miRNA-specific primer&#44; and 10<span class="elsevierStyleHsp" style=""></span>ng cDNA&#46; miRNA-specific primers from Qiagen were used &#40;<span class="elsevierStyleItalic">Homo sapiens</span> miR-33a&#44; Catalog no&#46; MS00003304&#59; and <span class="elsevierStyleItalic">Homo sapiens</span> miR-126-1&#44; Catalog No&#46; MS00003430&#41;&#46; The following PCR program was used&#58; 15<span class="elsevierStyleHsp" style=""></span>minutes of incubation at 95¿C &#40;to activate the Hot Start Taq DNA polymerase&#41; followed by 40 cycles of 15<span class="elsevierStyleHsp" style=""></span>seconds at 94¿C&#44; 30<span class="elsevierStyleHsp" style=""></span>seconds at 55¿C&#44; and 30<span class="elsevierStyleHsp" style=""></span>seconds at 70¿C&#46; The fluorescence emitted by SybrGreen was measured at the end of the extension step of each cycle&#46; The specificity of PCR amplification was determined by performing melt curve analysis of the amplicon once the PCR was completed&#46; This involved heating from 55¿C to 90¿C in increments of 0&#46;5¿C every 10<span class="elsevierStyleHsp" style=""></span>seconds&#46; Quantification was performed based on the results of 3 PCR reactions per sample from each participant in the control and patient groups&#46; The threshold cycle &#40;Ct&#41; was calculated using the qRT-PCR software&#44; and was defined as the point at which the amount of amplicon detected began to increase exponentially&#46; The results were normalized internally to the levels of miRNeasy Serum&#47;Plasma Spike-In Control Ce-miR-39&#95;1 &#40;Qiagen primer&#44; Catalog No&#46; MS00019789&#41;&#46; Relative transcript levels in each sample were calculated using the 2-<span class="elsevierStyleSup">&#916;&#916;</span>CT method&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ultrasonography</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; and controls &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41; underwent color Doppler ultrasonography &#40;Acuson Antares&#44; Siemens&#41; of the supra-aortic trunks using a 10-5<span class="elsevierStyleHsp" style=""></span>MHz transducer to detect atheromatous plaques&#44; as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;23</span></a> A carotid intima-media thickness &#40;IMT&#41;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#46;5<span class="elsevierStyleHsp" style=""></span>cm was considered indicative of the presence of a plaque&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistics</span><p id="par0050" class="elsevierStylePara elsevierViewall">Results are expressed as the median and interquartile range &#40;IQR&#41; unless otherwise specified&#46; Plasma expression levels of miRNAs were analyzed using the nonparametric Wilcoxon signed rank test to compare the median of the patient group with that of the control group&#46; Where indicated&#44; the Mann-Whitney test was used to analyze differences between patients and controls&#46; The Fischer test was used for the analysis of qualitative variables and the Spearman test to calculate correlations Differences were considered statistically significant at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05 &#40;GraphPad Prism version 5&#46;01&#44; GraphPad Software Inc&#46;&#41;&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethics</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study protocol was approved by the research and ethics committees of the hospital and research institute&#46;</p></span></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Clinical data</span><p id="par0060" class="elsevierStylePara elsevierViewall">The patient and control groups both consisted of 5 males and 6 females&#46; While the median age was somewhat higher in the patient group&#44; this difference was not statistically significant &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; All participants were white&#46; In the patient group the median disease activity scores &#40;PASI and BSA&#41; were<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; and the median duration of disease was 5 years&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The median IMT in patients was 0&#46;57<span class="elsevierStyleHsp" style=""></span>mm &#40;IQR&#44; 0&#46;54-0&#46;61&#41;&#44; as compared with 0&#46;50<span class="elsevierStyleHsp" style=""></span>mm in controls &#40;IQR&#44; 0&#46;48-0&#46;54&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0055&#41;&#46; One of the patients presented carotid atherosclerotic plaques&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">We observed no significant differences between patients and controls in levels of HDL-C&#44; LDL-C&#44; triglycerides&#44; glucose&#44; or insulin &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; One of the patients had metabolic syndrome according to ATP-III criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Positive correlations were detected between triglyceride levels and plasma levels of glucose &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;7900&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0038&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; insulin &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;8018&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0030&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and fibrinogen &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;6651&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0255&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46; LDL-C levels were correlated with disease duration &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;8219&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0019&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and HDL-C levels were inversely correlated with PASI score &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>-0&#46;6391&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0343&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; BMI &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>-0&#46;6273&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0388&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and systolic blood pressure &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>-0&#46;6651&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0255&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46; Analysis of obesity parameters revealed no differences in BMI&#44; ESR&#44; or waist circumference between patients and controls &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In the patient group we observed a correlation between BMI values and waist circumference &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;9091&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#44; glucose levels&#44; &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;6895&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0189&#41;&#44; and insulin levels &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;7973&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0033&#41;&#46; Levels of the inflammatory marker and coagulation protein fibrinogen were higher in patients vs controls &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Increased plasma levels of miR-33 in psoriasis patients</span><p id="par0075" class="elsevierStylePara elsevierViewall">We observed a significant increase in the relative plasma expression levels of miR-33 in psoriasis patients &#40;5&#46;34&#59; IQR&#44; 3&#46;12-7&#46;96&#41; with respect to controls &#40;2&#46;33&#59; IQR&#44; 1&#46;71-2&#46;84&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0049&#44; Wilcoxon signed rank test&#41;&#46; Plasma levels of miR-33 in 4 of the controls were too low to be correctly quantified&#44; and were thus quantified in only 7 of the 11 controls &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41; A positive correlation between plasma levels of miR-33 and insulin was observed in the patient group &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;7289&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0109&#41; but not in the control group &#40;r &#61; 0&#46;1071&#44; <span class="elsevierStyleItalic">P</span> &#61; &#46;8397&#44; n &#61; 7&#41;&#46; We detected no correlation in either group between plasma miR-33 expression and clinical parameters such as weight or BMI&#46; Insulin resistance &#40;IR&#41; was calculated by homeostasis model assessment &#40;HOMA&#41; using the following equation&#58; HOMA-IR &#61; &#91;insulin<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>glucose&#93;&#47;22&#46;5&#44; with insulin expressed in &#956;U&#47;mL and glucose in mmol&#47;L&#46; No differences in HOMA-IR were observed between patients &#40;1&#46;5&#59; IQR&#44; 1&#46;3-3&#46;4&#41; and controls &#40;1&#46;5&#59; IQR&#44; 1&#46;2-2&#46;02&#41; &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;&#46;4307&#44; Mann-Whitney test&#41;&#46; A positive correlation between plasma miRNA levels and HOMA-IR was observed in patients &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;6545&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0289&#41; but not in controls &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">-</span>0&#46;2143&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;6445&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">We observed no significant increase in the relative expression levels of miR-126 in the plasma of patients &#40;0&#46;5384&#59; IQR&#44; 0&#46;2839-1&#46;052&#41; vs controls &#40;0&#46;361&#59; IQR&#44; 0&#46;2806-0&#46;5371&#93;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0830&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">A negative correlation between levels of circulating miR-126 and IMT values was observed in patients &#40;r <span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>-0&#46;6181&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;0426&#41; but not in controls &#40;r<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>-0&#46;3333&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>&#46;3807&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Finally&#44; in the group of psoriasis patients we observed no significant correlations between plasma expression levels of miR-33 or miR-126 and the other clinical parameters analyzed&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The main finding of this study is that plasma levels of miR-33&#44; which is implicated in the posttranscriptional regulation of genes involved in cholesterol and glucose metabolism&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> are increased in patients with plaque psoriasis as compared with healthy controls and are positively correlated with plasma insulin levels and the HOMA-IR index value&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">There is currently growing interest in the study of circulating miRNAs given their potential as biomarkers&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Moreover&#44; circulating miRNAs may play a key role in intercellular communication&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> although this remains to be clarified&#46; miR-33a and miR-33b are encoded in the introns of the genes that encode sterol-regulatory element-binding protein 2 &#40;SREBP-2&#41;&#44; a transcription factor that binds to the sterol regulatory element&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> It has been reported that miR-33 plays a role in the posttranscriptional suppression of the cholesterol transporter ATP-binding cassette transporter A1 &#40;ABCA1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> leading to abnormal regulation of cholesterol efflux from macrophages&#46; Moreover&#44; manipulation of miR-33 levels may result in alterations in circulating HDL-C levels&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Similar results have been reported in mice lacking miR-33&#44; suggesting that blockade of this miRNA may help to prevent atherosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> miRNAs are gene regulatory molecules that target multiple mRNAs and regulate numerous cellular processes&#46; In hyperinsulinemia&#44; increases in the expression of SREBP transcription factors and miR-33 may contribute to increases and decreases in plasma levels of triglycerides and HDL-C&#44; respectively&#44; alterations that are included in the criteria for metabolic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Other described targets of miR-33 include genes involved in fatty acid oxidation and glucose metabolism<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#59; these include genes encoding insulin receptor substrate 2 and sirtuin 6 &#40;SIRT6&#41;&#8212;a nicotinamide adenine dinucleotide-dependent histone deacetylase implicated in molecular pathways involved in aging&#44; inflammation&#44; and cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> miR-33 also targets genes involved in the cell cycle&#44; cell proliferation&#44; and inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Moreover&#44; expression levels of miR-33 are inversely correlated with disease stage in bladder cancer patients&#44; in whom miR-33 targets transforming growth factor &#946; &#40;TGF-&#946;&#41; signaling pathways&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">AngiomiRs&#44; including miR-126&#44; are miRNAs found in plasma&#44; serum&#44; and circulating microvescicles that play key regulatory roles in vascular development and angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Patients with coronary artery disease or diabetes show reduced levels of circulating miR-126 as compared with healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Moreover&#44; treatment with etanercept decreases miR-126 expression in the serum of patients with psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> However&#44; in our study we found no significant differences in miR-126 levels between psoriasis patients and healthy controls&#44; although we did observe an inverse correlation between miR-126 expression and carotid IMT&#46; Only 1 of the psoriasis patients had atheromatous plaques and fulfilled the criteria for metabolic syndrome&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">We have presented significant findings that suggest an important biological role of miR-33 in psoriasis&#46; However&#44; the main limitation of our study is the small size of the sample&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In conclusion&#44; analysis of the expression of circulating miRNAs such as miR-33 in the plasma of psoriasis patients can contribute to a better understanding of the mechanisms underlying the systemic inflammatory alterations experienced by these patients&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Ethical Disclosures</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Protection of persons and animals</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals during the course of this study&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Data confidentiality</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their place of work concerning the publication of patient data and that all patients included in this study were appropriately informed and gave their written informed consent&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Right to privacy and informed consent</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0135" class="elsevierStylePara elsevierViewall">Funding was received from the European Social Fund &#40;European Commission-European Regional Development Fund &#91;ERDF&#47;FEDER&#93;&#41;&#59; CSIC-PI 200820I216 &#40;to M&#46;Z&#46;&#41;&#59; Junta de Andaluc&#237;a &#40;to J&#46;A&#46;&#41;&#59; the Department of Innovation&#44; Science&#44; and Enterprise and the Department of Science and Education &#40;CVI 226 and PC08-CTS-04 046 to J&#46;S&#46; and M&#46;Z&#46;&#41;&#59; ME-MICINN &#40;SAF-2008-03685&#41; &#40;to J&#46;S&#46; and M&#46;Z&#46;&#41;&#59; SAF-2011-27261 &#40;to J&#46;S&#46;&#41;&#59; JAE-Doc CSIC-FEDER &#40;postdoctoral contract to S&#46;G&#46;R&#46;&#41;&#59; and the Ministry for Equality&#44; Health and Social Policy of the Junta de Andalusia&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicts of Interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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            2 => "Psoriasis"
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            3 => "Media del grosor de la &#237;ntima carot&#237;dea"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Circulating microRNAs &#40;miRNA&#41; are involved in the posttranscriptional regulation of genes associated with lipid metabolism &#40;miRNA-33&#41; and vascular function and angiogenesis &#40;miRNA-126&#41;&#46; The objective of this exploratory study was to measure plasma levels of miRNA-33 and miRNA-126 in patients with plaque psoriasis and evaluate their association with clinical parameters&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We studied 11 patients with plaque psoriasis&#46; The median Psoriasis Area Severity Index &#40;PASI&#41; was 13 &#40;interquartile range &#91;IQR&#93;&#44; 9-14&#41; and body surface area involvement was 12 &#40;IQR&#44; 11-15&#41;&#46; Eleven healthy controls matched for age and sex were also included&#46; We analyzed cardiovascular risk factors and subclinical carotid atheromatosis&#46; Plasma miRNAs were evaluated using quantitative real-time polymerase chain reaction&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Carotid intima-media thickness was greater in patients &#40;&#46;57<span class="elsevierStyleHsp" style=""></span>mm&#59; IQR&#44; &#46;54-&#46;61&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; than in controls &#40;&#46;50<span class="elsevierStyleHsp" style=""></span>mm&#59; IQR&#44; &#46;48-&#46;54&#59; data available for 9 controls&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0055&#44; Mann-Whitney&#41;&#46; Expression of miRNA-33 in patients &#40;5&#46;34&#59; IQR&#44; 3&#46;12-7&#46;96&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; was significantly higher than in controls &#40;2&#46;33&#59; IRQ&#44; 1&#46;71-2&#46;84&#59; only detected in 7 of 11 controls&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0049&#44; Wilcoxon signed rank&#41;&#46; No differences in miRNA-126 levels were observed between patients and controls&#46; In patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; we observed a positive correlation between miRNA-33 and insulin levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;7289&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0109&#41; and a negative correlation between miRNA-126 and carotid intima-media thickness &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8211;&#46;6181&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0426&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In psoriasis patients plasma levels of lipid and glucose metabolism-related miRNA-33 are increased and correlated with insulin&#46; The study of circulating miRNA-33 in psoriasis may provide new insights about the associated systemic inflammatory abnormalities&#46;</p>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Se han identificado microARN &#40;miARN&#41; circulantes implicados en la regulaci&#243;n postranscripcional de genes del metabolismo de l&#237;pidos &#40;miARN-33&#41; y de la funci&#243;n vascular y angiog&#233;nesis &#40;miARN-126&#41;&#46; El objetivo de este estudio exploratorio ha sido evaluar los niveles plasm&#225;ticos de miARN-33 y miARN-126 en pacientes con psoriasis en placas y su relaci&#243;n con par&#225;metros cl&#237;nicos&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron once pacientes con psoriasis en placas &#40;PASI &#91;mediana&#93; &#91;25<span class="elsevierStyleCrossOut">-</span>75&#37; percentil&#93; 13 &#91;9-14&#93; y BSA 12 &#91;11-15&#93;&#41; y un grupo pareado en edad y sexo de 11 controles sanos&#46; Se analizaron factores de riesgo cardiovascular y la ateromatosis carot&#237;dea subcl&#237;nica&#46; Los miARN plasm&#225;ticos se evaluaron mediante la reacci&#243;n en cadena de la polimerasa cuantitativa a tiempo real &#40;qRT-PCR&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La media del grosor de la &#237;ntima carot&#237;dea &#40;GIM&#41; estaba aumentada en pacientes &#40;0&#44;57<span class="elsevierStyleHsp" style=""></span>mm &#91;0&#44;54-0&#44;61&#93;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; respecto a controles &#40;0&#44;50<span class="elsevierStyleHsp" style=""></span>mm &#91;0&#44;48-0&#44;54&#93;&#44; datos disponibles n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41; &#40;test Mann-Whitney&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0055&#41;&#46; La expresi&#243;n de miARN-33 en pacientes &#40;5&#44;34 &#91;3&#44;12&#8211;7&#44;96&#93;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; estaba significativamente aumentada respecto a controles &#40;2&#44;33 &#91;1&#44;71-2&#44;84&#93;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#59; solo se pudo detectar en 7 de 11&#41; &#40;test de Wilcoxon signed Rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0049&#41;&#46; No se observaron diferencias en los niveles de miARN-126 entre pacientes y controles&#46; En pacientes se observ&#243; una correlaci&#243;n positiva entre miARN-33 e insulina &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;7289&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0109&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#59; y una correlaci&#243;n negativa entre miARN-126 y GIM &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8211;0&#44;6181&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0426&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con psoriasis presentaban niveles plasm&#225;ticos aumentados de miARN-33 &#40;metabolismo de l&#237;pidos y glucosa&#41;&#44; que se correlacionaban con los niveles de insulina&#46; La valoraci&#243;n de miARN-33 circulante puede contribuir al conocimiento de las alteraciones inflamatorias sist&#233;micas en psoriasis&#46;</p>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">The two authors contributed equally&#46;</p>"
        "identificador" => "fn1"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Please cite this article as&#58; Garc&#237;a-Rodr&#237;guez S&#44; Arias-Santiago S&#44; Orgaz-Molina J&#44; Magro-Checa C&#44; Valenzuela I&#44; Navarro P&#44; et al&#46; Alteraciones en los niveles de expresi&#243;n del microARN-33 en plasma de pacientes con psoriasis 2014&#59;105&#58;497&#8211;503&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1095
            "Ancho" => 1628
            "Tamanyo" => 117947
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of miR-33a and miR-126 in each sample were calculated using the 2-<span class="elsevierStyleSup">&#916;&#916;</span>CT method<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> &#40;see Materials and Methods&#41;&#46; Results are presented as the median and interquartile range in logarithmic scale &#40;base 10&#41;&#46; Anti-logarithmic values are indicated in the vertical axes&#46; The Wilcoxon signed rank test was used to compare the median of the patient group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; with that of the control group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46; Plasma levels of miR-33 expression were lower in controls than in psoriasis patients &#40;a&#41;&#46; Plasma miR-33 levels were quantified in 7 of the 11 controls studied &#40;see Results&#41;&#46; Analyses were performed using Graph-Pad Prism software &#40;version 5&#46;01&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ESR&#44; erythrocyte sedimentation rate&#59; HDL-C&#44; high-density lipoprotein cholesterol&#59; IMT&#44; intima-media thickness&#59; LDL-C&#44; low-density lipoprotein cholesterol&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Psoriasis Patients &#40;Ps&#41;&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Controls &#40;C&#41;&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;Ps vs C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;Male<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;55&#41;&#47;5 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;55&#41;&#47;5 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;y&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;25-42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;26-42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;6924&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disease duration &#40;y&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;1-18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PASI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;9-14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BSA &#40;maximum&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;11-15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Carotid IMT &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;57 &#40;0&#46;54-0&#46;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;50 &#40;0&#46;48-0&#46;54&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ESR &#40;mm&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;6-11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;5-7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0743&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C-reactive protein &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;1 &#40;0&#46;17-2&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;21 &#40;0&#46;05-1&#46;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;1579&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Body mass index &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;33 &#40;23&#46;8-31&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;53 &#40;20&#46;49&#8211;26&#46;72&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0620&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Waist circumference &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male88 &#40;80&#46;3-109&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male92 &#40;92-98&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5556&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female99&#46;8 &#40;84&#46;3-108&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female81&#46;5 &#40;76-94&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0777&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serum triglyceride levels &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;54-112&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;77-150&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;2643&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HDL-C &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Male49 &#40;41&#46;5-72&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male51 &#40;41-63&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female57 &#40;46&#46;8-114&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female74 &#40;66-83&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4848&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LDL-C&#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">133 &#40;67-160&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127 &#40;114-154&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7676&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucose &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84 &#40;78-103&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;62-88&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;1577&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Insulin &#40;&#956;U&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;3 &#40;7-13&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;2 &#40;7&#46;1-10&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8954&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systolic blood pressure &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120 &#40;107-126&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">123 &#40;114-131&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3783&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diastolic blood pressure&#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">73 &#40;66-82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">73 &#40;70 to 86&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4579&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fibrinogen &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">389 &#40;375-456&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">304 &#40;243-345&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Mann-Whitney test for comparative analysis between the control and psoriasis patient groups&#46;</p>"
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              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Number of controls and psoriasis patients studied&#46; Data in parentheses are percentages&#46;</p>"
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              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Data available for only 9 of the 11 controls&#46;</p>"
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              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Data available for only 10 of the 11 controls&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Clinical Data<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>"
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      "titulo" => "References"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psoriasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46;O&#46; Nestle"
                            1 => "D&#46;H&#46; Kaplan"
                            2 => "J&#46; Barker"
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                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1056/NEJMra0804595"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2009"
                        "volumen" => "361"
                        "paginaInicial" => "496"
                        "paginaFinal" => "509"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19641206"
                            "web" => "Medline"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Garcia-Rodriguez"
                            1 => "S&#46; Arias-Santiago"
                            2 => "R&#46; Perandr&#233;s-L&#243;pez"
                            3 => "L&#46; Castellote"
                            4 => "E&#46; Zumaquero"
                            5 => "P&#46; Navarro"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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                      "Revista" => array:6 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23457721"
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              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psoriasis genetics&#58; Breaking the barrier"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;D&#46; Roberson"
                            1 => "A&#46;M&#46; Bowcock"
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                    0 => array:2 [
                      "doi" => "10.1016/j.tig.2010.06.006"
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                      "titulo" => "Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63&#44;100-element oligonucleotide array"
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                            2 => "M&#46;C&#46; Kao"
                            3 => "E&#46; Lee"
                            4 => "F&#46; Du"
                            5 => "A&#46; Menter"
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                    0 => array:2 [
                      "doi" => "10.1152/physiolgenomics.00157.2002"
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                            0 => "E&#46; Sonkoly"
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                            2 => "P&#46;C&#46; Janson"
                            3 => "A&#46; Saaf"
                            4 => "L&#46; Lundeberg"
                            5 => "M&#46; Tengvall-Linder"
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                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0000610"
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                    0 => array:2 [
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Xu"
                            1 => "P&#46; Brodin"
                            2 => "T&#46; Wei"
                            3 => "F&#46; Meisgen"
                            4 => "L&#46; Eidsmo"
                            5 => "N&#46; Nagy"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/jid.2011.55"
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                            0 => "F&#46; Meisgen"
                            1 => "N&#46; Xu"
                            2 => "T&#46; Wei"
                            3 => "P&#46;C&#46; Janson"
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                            5 => "O&#46; Broom"
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                    0 => array:2 [
                      "doi" => "10.1111/j.1600-0625.2012.01462.x"
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2014.04.003

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	8	14	22
2024 October	66	39	105
2024 September	71	29	100
2024 August	88	56	144
2024 July	72	31	103
2024 June	72	32	104
2024 May	83	36	119
2024 April	79	31	110
2024 March	87	28	115
2024 February	60	36	96
2024 January	62	39	101
2023 December	63	15	78
2023 November	70	28	98
2023 October	67	34	101
2023 September	68	32	100
2023 August	34	14	48
2023 July	60	33	93
2023 June	56	26	82
2023 May	65	22	87
2023 April	34	34	68
2023 March	44	27	71
2023 February	48	24	72
2023 January	46	26	72
2022 December	54	46	100
2022 November	55	26	81
2022 October	33	23	56
2022 September	20	35	55
2022 August	31	27	58
2022 July	34	46	80
2022 June	28	25	53
2022 May	39	41	80
2022 April	39	43	82
2022 March	62	50	112
2022 February	49	35	84
2022 January	44	43	87
2021 December	28	40	68
2021 November	55	46	101
2021 October	55	59	114
2021 September	30	45	75
2021 August	45	25	70
2021 July	30	33	63
2021 June	27	32	59
2021 May	32	28	60
2021 April	85	43	128
2021 March	67	22	89
2021 February	36	19	55
2021 January	53	16	69
2020 December	31	15	46
2020 November	19	12	31
2020 October	32	12	44
2020 September	49	12	61
2020 August	33	23	56
2020 July	26	13	39
2020 June	30	20	50
2020 May	37	14	51
2020 April	34	26	60
2020 March	26	18	44
2020 February	14	1	15
2020 January	4	0	4
2019 December	8	2	10
2019 November	4	1	5
2019 September	6	2	8
2019 August	6	0	6
2019 July	4	2	6
2019 June	4	2	6
2019 May	6	10	16
2019 April	2	2	4
2019 March	2	4	6
2019 February	4	0	4
2019 January	3	0	3
2018 November	3	0	3
2018 October	4	0	4
2018 September	3	0	3
2018 March	0	4	4
2018 February	22	1	23
2018 January	42	16	58
2017 December	42	8	50
2017 November	37	17	54
2017 October	33	12	45
2017 September	29	16	45
2017 August	32	17	49
2017 July	35	16	51
2017 June	33	14	47
2017 May	44	10	54
2017 April	35	17	52
2017 March	26	9	35
2017 February	35	14	49
2017 January	17	8	25
2016 December	43	18	61
2016 November	54	9	63
2016 October	57	27	84
2016 September	69	14	83
2016 August	55	9	64
2016 July	29	13	42
2016 June	7	12	19
2016 May	8	5	13
2016 April	3	5	8
2016 March	4	3	7
2016 February	12	3	15
2016 January	10	1	11
2015 December	14	6	20
2015 November	4	1	5
2015 October	12	2	14
2015 September	6	8	14
2015 August	19	3	22
2015 July	49	15	64
2015 June	39	8	47
2015 May	38	12	50
2015 April	29	11	40
2015 March	31	11	42
2015 February	35	12	47
2015 January	63	7	70
2014 December	34	9	43
2014 November	37	11	48
2014 October	33	12	45
2014 September	41	10	51
2014 August	28	17	45
2014 July	23	23	46
2014 June	23	14	37
2014 May	2	1	3

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