Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

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.

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

“…Another miRNA negatively correlated with cholesterol, miR-374a-5p, is able to regulate the expression of many target genes involved in carbohydrates and lipids biosynthesis and inflammation, particularly interleukin-17A, in turn, involved in lipid metabolism ( Yu et al, 2014 ; Doumatey et al, 2018 ). Also, miR-1277-5p and miR-1273c have been reported as altered in inflammatory statuses ( Zalewski et al, 2020 ). Altogether, the observed anti-correlations between cholesterol intake and these miRNAs suggest that cholesterol itself could participate in the regulation of its efflux in macrophages, as recently reported for HDL ( Orekhov et al, 2018 ).…”

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm

“…The study design, methodology, article structure and language have been inspired by our previous studies regarding deregulation of miRNA regulatory network in lower extremities arterial disease [ 28 ] and chronic venous disease [ 29 ].…”

Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens

“…Many studies have identified dysregulations of gene expression associated with vascular cell functions, including cell differentiation, proliferation, migration, and apoptosis exhibiting modulatory function of angiogenesis, endothelial cells dysfunction and response for ischemic events and oxidative stress [ 26 , 27 , 28 , 29 , 30 , 31 ]. Alterations in expression of numerous genes are considered as potential signatures of vascular diseases including atherosclerosis [ 32 , 33 , 34 ], LEAD [ 35 , 36 , 37 ], AAA [ 38 , 39 , 40 , 41 , 42 ] and CVD [ 43 , 44 , 45 , 46 ].…”

“…Therefore, transcriptomic patterns of PBMCs subpopulations originating from patients with LEAD, AAA and CVD versus healthy subjects were previously compared and potential transcriptomic biomarkers of these diseases were proposed [ 37 , 42 , 46 ]. In the current study, pairwise comparison of gene expression profiles between LEAD, AAA and CVD were performed in order to identify transcriptomic similarities and differences of these conditions.…”

“…The study design, methodology and language were inspired by our previous studies regarding dysregulation of microRNA (miRNA) regulatory network in LEAD [ 37 ], AAA [ 42 ] and CVD [ 46 ] compared to healthy controls.…”