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Transcriptomic analysis of human varicose veins

ABSTRACT: tRNA-derived fragments (tRFs) with a size of 15-50 nt are derived from mature or precursor tRNAs and associated with a variety of pathological conditions. However, the roles of tRFs in varicose veins (VVs) are largely unknown. The aim of this study was to identify the tRFs involved in VVs and predict their potential biological functions. We first performed small RNA-seq to investigate the expression profiles of tRFs in vascular tissue of VVs patients and healthy controls. In total, 13,789 tRFs were obtained, accounting for 4 % of the total small RNA. Moreover, 45 tRFs were remarkably changed, of which 14 were up-regulated and 31 were down-regulated. Gene Ontology analysis showed that the target genes of these differently expressed tRFs are mainly involved in transcriptional functions, DNA-template and nervous system development. Kyoto Encyclopedia of Genes and Genomes analysis revealed that target genes of these differently expressed tRFs were significantly enriched the wnt signaling pathway and the calcium signaling pathway which regulate local hypoxia and degradation of extracellular matrix(ECM) processes, which play an important role in the development of VVs. Furthermore, differentially expressed mRNA-tRF-non coding RNA regulatory network was constructed which revealed that tRFs may play a central role in this interaction network and correlate with many mRNAs and ncRNAs. Additionally, two up-regulated tRFs (tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY) and one down-regulated tRFs (tRF-40-86J8WPMN1E8Y7Z2R)) were identified and verified. These results show that tRFs are aberrantly expressed in vascular tissue of patients with VVs and might play important roles in the development of VVs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122109 | GEO | 2020/11/06

REPOSITORIES: GEO

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Project description:BACKGROUND: As evidenced by epidemiological and etiological studies, the development of varicose veins is driven by risk-factors which support the development of venous hypertension and thus chronically augment circumferential stress of the venous wall (e.g. dysfunctional venous valves, pregnancy or obesity). We have previously verified the relevance of this biomechanical stimulus for the activation of venous endothelial as well as smooth muscle cells and the subsequent detrimental structural remodeling of the vein wall in experimental mouse models. METHODS: Here, transcriptome analyses revealed an increase in the expression of cyclooxygenase 2 (COX-2) in human venous endothelial cells upon exposure to biomechanical stress. Subsequently, we investigated the impact of diclofenac – a cyclooxygenase inhibitor – on responses of isolated mouse veins to augmented wall stress in vitro and on varicose-like venous remodeling in vivo. RESULTS: Diclofenac treatment decreased COX-2 protein abundance in mouse veins but had no significant impact on the expression of corresponding transcripts. Short-term exposure to elevated pressure levels stimulated the activity of matrix-metalloproteinase-2 (MMP-2) and mitogen activated protein kinases ERK1/2. Diclofenac decreased the level of activated MMP-2 and ERK1/2 in pressure-exposed mouse veins. Varikose-like remodeling of veins in the mouse auricle was significantly inhibited by transdermal application of diclofenac-containing phospholipid-micelles. This effect was associated with decreased COX-2 and MMP-2 abundance as well as cell proliferation. CONCLUSION: The cyclooxygenase inhibitor diclofenac interferes with short term activation of MAP-kinases and matrix-metalloproteinases in cells of the wall stress-exposed venous wall while attenuating venous remodeling in vivo. Thus, nonsteroidal anti-inflammatory drugs may be suitable to interfere with processes promoting the progression of varicose vein development and biomechanical activation of venous cells.

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Transcriptomic analysis of human varicose veins

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