MicroRNA Profiling in Great Saphenous Vein Tissues of Patients with Chronic Venous Insufficiency

Abstract

Chronic venous insufficiency (CVI) is a common disease characterized by structural and functional abnormalities of the venous system. Until recently, the pathogenesis of CVI remains largely unknown. MicroRNAs (miRNAs) are a family of endogenous small non-coding RNAs emerged as post-transcriptional gene repressors and play essential roles in diverse pathological processes including vascular disease. However, their roles in CVI have not been elucidated. In this study, we employed oligonucleotide microarrays to perform a genome-wide miRNAs profiling in the great saphenous vein (GSV) tissues of patients with CVI. Our results revealed a total of 14 miRNAs that are expressed differentially in GSV tissues. Among them nine miRNAs were found significantly up-regulated, while five miRNAs were downregulated significantly. Real-time RT-PCR verified statistically consistent expression of three selected miRNAs (miR-34a, miR-155 and miR-202) with microarrays analysis. These three miRNAs, which were described as crucial regulators in many biological processes and vascular diseases, might also play important roles in CVI. Functional annotation of target genes of differentially expressed miRNAs via bioinformatics approaches revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for CVI, including mitogen-activated protein kinase pathways, pathways in cancer, apoptosis, and cell cycle, and p53 signaling pathways. In summary, miRNAs might involve in multiple signaling pathways contributing to the pathological processes of CVI. These data may provide fundamental insights into the molecular basis of CVI, which may aid in designing novel approaches for prevention and treatment of this complex disease.Keywords: bioinformatics; chronic venous insufficiency; great saphenous vein; microarray; microRNA Tohoku J. Exp. Med., 2012 Dec, 228 (4), 341-350. © 2012 Tohoku University Medical Press Chronic venous insufficiency (CVI) is a complex medical condition characterized by structural and functional abnormalities of the venous system, which is commonly seen in humans. CVI is manifested with a range of signs, including varicose veins, trophic skin changes and venous ulcers. It has a considerable socioeconomic impact in many countries due to its high prevalence, cost of investigations and management, deterioration of the quality of life and loss of working days (Rabe and Pannier 2010). To date, in spite of numerous studies on CVI, the etiology and pathogenesis of CVI remains largely unknown.MicroRNAs (miRNAs) are a family of highly conserved, endogenous small non-coding RNAs (19-24nt) that post-transcriptionally repress gene expression via degradation or translational inhibition of their target mRNAs. They play important roles in nearly all physiological and pathological processes, including cell differentiation, proliferation, apoptosis, cardiovascular disease, and human cancers (Bartel 2004). There is mounting evidence suggesting that miRNAs had distinct expression profiles an...

Augmentation of miR‐202 in varicose veins modulates phenotypic transition of vascular smooth muscle cells by targeting proliferator–activated receptor‐γ coactivator‐1α

“…Our previous results from a miRNA array have shown that miR-202 was significantly upregulated in the media of varicose veins (data not shown), which was consistent with another study. 16 In this study, we used real-time quantitative polymerase chain reaction to compare the expression of miR-202 between 33 varicose veins, graded from Classes 3 to 6, and 33 adjacent normal segments from the same patient. The results showed that miR-202 expression significantly increased in the vessel media of varicose veins ( Figure 1A).…”

“…miR‐133, miR‐663, miR‐145, and miR‐195 have been shown to regulate the VSMC phenotype. Analysis of human great saphenous vein tissues using microarrays showed increased miR‐202 in patients with chronic venous insufficiency . miR‐202 also has been implicated in multiple cancers and tissue development .…”

Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

“…To date, the topic of miRNA and gene expression analysis in venous disorders has not been sufficiently studied [33,34]. Cui et al used microarray and RT-PCR to research upregulation of miR-34a, miR-202 and downregulation of miR-155 in vein biopsies from patients with CVI [33].…”

“…Altered expression patterns of miRNAs and genes were demonstrated in vein specimens derived from patients with CVI and compared to healthy subjects [32,33]. Dysregulation of miRNA expression, reported in venous ulcers biopsies, has been associated with inhibition of wound healing [34].…”

Weighted Gene Co-expression Network Analysis for RNA-Sequencing Data of the Varicose Veins Transcriptome

“…Kim et al (2005) recognized 3 cDNAs and Görmüs et al (2014) found that up-regulation of elastin and related genes may play an important role in the pathogenesis of varicose veins. Cui et al (2012) carried out microRNAs (miRNAs) profiling in the GSV in patients with chronic venous insufficiency (CVI) and found that miR-34a, miR-155, and miR-202 might play crucial rules in CVI and varicose veins. Li et al (2014) reported the aberrantly expressed long non-coding RNAs (lncRNAs) involved in varicose veins and predicted their potential functions.…”