miRNA‑92a inhibits vascular smooth muscle cell phenotypic modulation and may help prevent in‑stent restenosis

Abstract

The modulation of vascular smooth muscle cell (VSMc) phenotype during cellular proliferation and migration may represent a potential therapeutic approach for vascular intimal hyperplasia prevention. However, the precise role of this process in VSMc biology and remodeling remains unclear. in the present study, western blotting, Pcr, MTT and Transwell assays were used to analyze related protein and mrna expression, cell viability and cell migration, respectively. it was demonstrated that mir-92a modulated VSMcs into a synthetic phenotype via the Kruppel-like factor 4 (KlF4) pathway. Targeting microrna (mirna/mir)-92a in VSMcs using a KlF4 inhibitor suppressed the synthetic phenotype and inhibited VSMc proliferation and migration. To further confirm this finding, the expression levels of miR-92a were measured in patients undergoing coronary artery intervention. The serum miR-92a expression levels were significantly higher in patients with in-stent restenosis (iSr) compared with those in patients without iSr, whereas KlF4 expression was significantly reduced in the non-iSr group. Bioinformatic analysis and promoter-luciferase reporter assays were used to examine the regulatory mechanisms underlying KlF4 expression. KlF4 was demonstrated to be transcriptionally upregulated by mir-92a in VSMcs. mirna transfection was also performed to regulate the level of mir-92a expression. mir-92a overexpression inhibited VSMc proliferation and migration, and also increased the mrna and protein expression levels of certain differentiated VSMc-related genes.Finally, mir-92a inhibition promoted the proliferation and migration of VSMcs, which could be reversed using a KlF4 inhibitor. collectively, these results indicated that the local delivery of a KlF4 inhibitor may act as a novel therapeutic option for the prevention of iSr.

Extracellular vesicles in atherosclerosis and vascular calcification: the versatile non-coding RNAs from endothelial cells and vascular smooth muscle cells

“…Uremic toxins accumulation upregulated the expression level of miR-92a-3p in ECs, contributing to endothelial dysfunction ( 93 ). MiR-92a-3p overexpression inhibited VSMCs proliferation and migration, while miR-92a-3p inhibition promoted the proliferation and migration of VSMCs via the KLF4 pathway ( 94 , 95 ). MiR-92a-3p encapsulation in EC-EVs demonstrated a double effect on AS when recipient cells assimilate it: it promoted ECs phenotype switching while it inhibited VSMCs proliferation and migration.…”