Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease.

Daniel P Zalewski,Przemysław Kołodziej,Janusz Kocki,Andrzej Stępniewski,Karol P Ruszel,Dariusz Gałkowski,Anna Bogucka-Kocka,Paulina Chmiel,Łukasz Komsta,Tomasz Zubilewicz,Marcin Feldo,Jacek Bogucki

doi:10.3390/jcm9051251

Abstract

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

Highlights

Chronic Venous Disease (CVD) is a common vascular disease of the lower limbs
Chronic Venous Insufficiency (CVI) is a term reserved for advanced CVD, which is applied to functional abnormalities of the venous system producing edema, skin changes, or venous ulcers (C3–C6 in CEAP classification) [3]
A statistically significant difference between these groups was observed in age (p = 8.387 × 10−3) and smoking history (p = 1.296 × 10−4), which probably results from inclusion of healthy CVD-negative non-smoking individuals in control group

Summary

Introduction

Chronic Venous Disease (CVD) is a common vascular disease of the lower limbs. CVD is defined as a syndrome of chronic morphological and functional abnormalities of the venous system, manifested either by symptoms (including tingling, aching, burning, pain, muscle cramps, swelling, sensations of throbbing or heaviness, itching, restless legs, leg tiredness and fatigue) or clinical signs prompting the need for investigation and medical care [3]. The disease encompasses a wide spectrum of clinical presentations such as telangiectasia, varicose veins, leg edema, skin changes and ulcers, as included in the Clinical, Etiology, Anatomic, Pathophysiology (CEAP) classification [4,5,6]. Chronic Venous Insufficiency (CVI) is a term reserved for advanced CVD, which is applied to functional abnormalities of the venous system producing edema, skin changes, or venous ulcers (C3–C6 in CEAP classification) [3]

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