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

A Magenta,M Napolitano,G Melillo,M D’Agostino,F Martino,L Di Vito,M C Capogrossi,D Abeni,C Uras,C Albanesi,S Madonna,F Barillà,S Sileno

doi:10.1155/2019/8061901

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.

Highlights

Psoriasis is a chronic inflammatory disease in which both genetic and environmental factors play an important pathogenic role
The two groups were homogeneous for clinical, anthropometric, and laboratory parameters with the exception of total cholesterol values that were higher in Pso vs. Ctrl, in agreement with lipid abnormalities associated with this disease [15, 42, 43]
Erythrocyte sedimentation rate (ESR) was higher in Pso compared to Ctrl, and erythrocyte sedimentation rate (ESR) is a delayed inflammatory biomarker known to increase in Pso [44]

Summary

Introduction

Psoriasis is a chronic inflammatory disease in which both genetic and environmental factors play an important pathogenic role. Life expectancy is reduced in severe psoriasis by up to 4 years, largely because of the high incidence of CVD and CeVD [6,7,8]. It is still debated whether psoriasis may be regarded as an independent risk factor for CVD [9], as patients with severe psoriasis have a higher prevalence of traditional cardiovascular (CV) risk factors, including smoking, dyslipidemia, diabetes, and hypertension [7, 10, 11]. Systemic inflammation may induce atherosclerosis progression [12] and in severe psoriasis is associated with an elevated production of oxygen free radicals, which in turn induce vascular endothelial cell (EC) damage

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