microRNA-491-5p protects against atherosclerosis by targeting matrix metallopeptidase-9

Abstract

AbstractAbnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are critical processes that are involved in atherosclerosis. The aim of this study was to explore the role of microRNA-491-5p (miR-491-5p) in the progression of atherosclerosis by regulating the growth and migration of VSMCs. In this study, we showed that the expression of miR-491-5p was downregulated in the atherosclerotic plaque tissues and plasma samples of the patients with atherosclerosis. The bioinformatic analysis and dual-luciferase reporter assay identified that matrix metallopeptidase-9 (MMP-9) was a target gene of miR-491-5p. The results showed a significant upregulation of MMP-9 in the atherosclerotic plaque tissues and plasma samples. Subsequently, the results also showed that downregulation of miR-491-5p significantly promoted the proliferation and migration of VSMCs and inhibited the apoptosis in VSMCs. Furthermore, we detected the effects of miR-491-5p mimic on the growth and migration of VSMCs, and the results illustrated that miR-491-5p mimic could inhibit the proliferation and migration of VSMCs and promote the apoptosis of VSMCs. Notably, MMP-9 plasmid could reverse all the effects of miR-491-5p mimic on VSMCs. Collectively, our study provides the first evidence that miR-491-5p inhibited the growth and migration of VSMCs by targeting MMP-9, which might provide new biomarkers and potential therapeutic targets for atherosclerosis treatment.