P4442miR-200c is up-regulated in lesional skin and plasma of patients affected by psoriasis and correlates with disease severity and cardiovascular risk

Abstract Background Psoriasis is a common, chronic inflammatory disease involving skin. Psoriatic patients mostly show the plaque-type clinical form and several comorbidities, including cardiovascular (CV) diseases. We previously showed that miR-200 family members (miR-200s) is induced by reactive oxygen species (ROS). miR-200c is the most up-regulated member and is responsible for apoptosis, senescence, endothelial dysfunction, ROS increase and nitric oxide decrease. Circulating miR-200c is upregulated in Familial Hypercholesterolemia in children, a pathology associated with ROS increase and atherosclerosis. miR-200c increases also in carotid plaques and plasma of atherosclerotic pts vs healthy subjects and positively correlates with plaque instability biomarkers. Purpose Given the role of miR-200s in ROS modulation, endothelial dysfunction, cardiac remodelling and inflammation, all features associated with psoriasis, we wondered whether miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and whether miR-200 levels correlated with CV risk. Methods 29 Pso were compared to 29 control subjects (Ctrl) age- and sex-matched. All Pso had a severe psoriasis, defined as Psoriasis Area and Severity Index (PASI) >10 and one of the following: at least two systemic psoriasis treatments, psoriasis onset <40 years of age, disease duration >10 years. Exclusion criteria were: diabetes, cerebrovascular events, myocardial infarction, and/or myocardial revascularization, psoriatic arthritis. Total RNA was extracted from plasma and miR-200 levels assayed by quantitative real-time PCR. The clinical parameters were similar between the two groups except for Total Cholesterol (mg/dl) (Ctrl 193.3±6.2; Pso 213.2±6.9; P<0.05). Blood pressure measurement, wave reflection analysis and pulse wave velocity (PWV) were similar between groups, echocardiographic parameters were different for left ventricular (LV) mass index (g/m2) (Ctrl 84.2±5.2; Pso 102.5±4.7; P<0.05) and relative wall thickness (RWT) (Ctrl 0.4±0.0; Pso 0.48±0.0; P<0.01). Total RNA was extracted from biopsies of nonlesional (NLS) and LS of 6 Pso and 6 healthy subject skin (HS). Results miR-200s were increased in LS vs NLS samples. miR-200c was the most expressed and was upregulated also in LS vs HS (2.0+0.2 fold-increase; P<0.01). Circulating miR-200c (2.5+0.5 fold-increase; P<0.05) and miR-200a (4.8+0.7 fold; P<0.0001) were up-regulated in Pso vs Ctr. Circulating miR-200c positively correlated with LV mass (Rs=0.32; P<0.05), RWT (Rs=0.32; P<0.05) and diastolic dysfunction assessed with E/e' parameters (Rs=0.34; P<0.05). Circulating miR-200a correlated only with LV mass, although not significantly (Rs=0.30; P=0.06). miR-200c exhibited a significant positive correlation with PASI (Rs=0.43; P<0.05) and with disease duration of (Rs=0.40; P<0.05). Conclusion miR-200c is upregulated in skin plaques and plasma of Pso, and might be involved in inflammatory and CV risk increase in these patients. Acknowledgement/Funding Ministero della Salute RF-2016-02362708 to AM and MCC