The Oxidative Stress-Induced miR-200c Is Upregulated in Psoriasis and Correlates with Disease Severity and Determinants of Cardiovascular Risk

Abstract

Psoriasis is a chronic inflammatory skin disease associated with reactive oxygen species (ROS) increase and a higher risk of cardiovascular (CV) events. We previously showed that the miR-200 family (miR-200s) is induced by ROS, miR-200c being the most upregulated member responsible for apoptosis, senescence, ROS increase, and nitric oxide decrease, finally causing endothelial dysfunction. Moreover, circulating miR-200c increases in familial hypercholesterolemic children and in plaques and plasma of atherosclerotic patients, two pathologies associated with increased ROS. Given miR-200s' role in endothelial dysfunction, ROS, and inflammation, we hypothesized that miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and that their levels correlated with some CV risk determinants at a subclinical level. All Pso had severe psoriasis, i.e., Psoriasis Area and Severity Index (PASI) > 10, and one of the following: at least two systemic psoriasis treatments, age at onset < 40 years, and disease duration > 10 years. RNA was extracted from plasma (Pso, N = 29; Ctrl, N = 29) and from nonlesional skin (NLS) and LS of 6 Pso and 6 healthy subject skin (HS) biopsies. miR-200 levels were assayed by quantitative RT-PCR. We found that all miR-200s were increased in LS vs. NLS and miR-200c was the most expressed and upregulated in LS vs. HS. In addition, circulating miR-200c and miR-200a were upregulated in Pso vs. Ctrl. Further, miR-200c positively correlated with PASI, disease duration, left ventricular (LV) mass, LV relative wall thickness (RWT), and E/e', a marker of diastolic dysfunction. Multiple regression analysis indicates a direct association between miR-200c and both RWT and LV mass. Circulating miR-200a correlated positively only with LV mass and arterial pressure augmentation index, a measure of stiffness, although the correlations were nearly significant (P = 0.06). In conclusion, miR-200c is upregulated in LS and plasma of Pso, suggesting its role in ROS increase and inflammation associated with CV risk in psoriasis.