MiR-210 regulates vascular endothelial cell apoptosis in arteriosclerosis obliterans through the JAK1-STAT3 pathway

Abstract

IntroductionAtherosclerosis is a continuously worsening chronic condition that starts in the arteries and may then affect other blood vessels. There is increasing evidence linking microRNAs to the development of arteriosclerosis obliterans (ASO). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied in this study to detect miR-210-5p (miR-210) expression, and significant upregulation was observed in human arterial walls where ASO was prevalent.Material and methodsThe proliferation of human umbilical vascular endothelial cells (HUVECs) with various levels of miR-210 expression was assessed via MTT and colony-formation assays. Cell proliferation was significantly promoted in HUVECs with upregulated miR-210 levels and reduced in HUVECs with downregulated miR-210 levels.ResultsFlow cytometric analysis of cells stained with annexin V-FITC and propidium iodide data demonstrated that miR-210 inhibited apoptosis, while miR-210 inhibition promoted apoptosis by mediating pro-apoptotic protein expression levels. These results were verified using a dual-luciferase reporter gene assay system, which showed that Janus kinase 1 (JAK1) was directly targeted by miR-210, while an miR-210 mimic significantly decreased downstream JAK1 and signal transducer and activator of transcription 3 (STAT3) activation at a post-transcriptional level in HUVECs, as detected by western blotting and qRT-PCR. Further inhibition of either JAK1 or STAT3 counteracted the effect of miR-210 on HUVEC proliferation and apoptosis. These findings suggest that miR-210 promotes HUVEC proliferation, at least in part, by targeting the JAK1-STAT3 signaling axis.ConclusionsThis study provides insights into the contribution of the miR-210-JAK1-STAT3 axis and its underlying mechanisms to ASO pathology.