Effect of microRNA‑133a‑3p/matrix metalloproteinase‑9 axis on the growth of atherosclerotic vascular smooth muscle cells

Abstract

Atherosclerosis (AS) is the leading cause of cardiovascular disease and poses a threat to human health. MicroRNAs (miRNAs/miRs) are a group of endogenous small non-coding RNAs that have been identified to serve important roles in AS. However, the expression and role of miR-133a-3p in AS remains unclear. The aim of the present study was to investigate miR-133a-3p in AS and to determine its underlying mechanism. The level of miR-133a-3p expression in the blood and vascular plaque tissue of patients with AS was detected via reverse transcription-quantitative PCR (RT-qPCR). The role of miR-133a-3p in human vascular smooth muscle cells (hVSMCs) was investigated, following upregulation and downregulation of this miR in hVSMCs. Cell proliferation and apoptosis were determined using a Cell Counting kit-8 assay and flow cytometry, respectively. The results demonstrated the downregulation of miR-133a-3p in the blood and vascular plaque tissue of patients with AS. Matrix metallopeptidase-9 (MMP-9) was revealed to be a direct target gene of miR-133a-3p, which was upregulated in the blood and vascular plaque tissue of patients with AS. Furthermore, MMP-9 was determined to be negatively regulated by miR-133a-3p in hVSMCs. In addition, significant inhibition of hVSMC proliferation and induction of cell apoptosis were observed following MMP-9 downregulation and following transfection with the miR-133a-3p mimic. The effects of the miR-133a-3p mimic on hVSMC proliferation and apoptosis were reversed by MMP-9 over-expression. Overall, the results indicated that miR-133a-3p was downregulated in AS, which results in the inhibition of hVSMC proliferation and the induction of cell apoptosis via MMP-9. miR-133a-3p may therefore be a promising therapeutic target for the treatment of AS.

Diagnostic and Predictive Values of Circulating Extracellular Vesicle-Carried microRNAs in Ischemic Heart Disease Patients With Type 2 Diabetes Mellitus

“…Previous studies on miR-155-5p demonstrated a significant down-regulation in peripheral blood mononuclear cells and whole blood from patients with diabetes ( 36 ). Additionally, the expression level of circulating miR-133a-3p is also shown to be significantly down-regulated in patients with diabetes compared with controls ( 37 ), which results in the inhibition of human vascular smooth muscle cell proliferation and the induction of cell apoptosis via matrix metalloprotein-9 (MMP-9) ( 38 ). In the present study, we found that EV-carried miR-155-5p and miR-133a-3p are significantly down-regulated in IHD-DM patients compared to healthy controls.…”

MicroRNAs Expression Profiles in Platelet-Derived Exosomes From Coronary In-Stent Restenosis and the Potential Markers

“…Additionally we further veri ed this observation using the blood of select clinical patients, which showed that the results were consistent. Prior studies have shown that the miR-133a-3p, which is down-regulated in atherosclerosis, inhibits the proliferation, but induces apoptosis of human vascular smooth muscle cell (hVSMC) in MMP-9 dependent mechanisms [26]. In the BV2 cells treated with lipopolysaccharide (LPS) or chylomicrons (CM) after ischemia and reperfusion, miRNA-589 expression was found to be down-regulated, while overexpression of miRNA-589 decreased the release of in ammatory cytokines by targeting TRAF6 [27].…”

miR‐217 alleviates high‐glucose‐induced vascular smooth muscle cell dysfunction via regulating ROCK1

“…For example, miR‐133a‐3p, which is significantly downregulated in blood samples and AS plaques of AS patients, can induce apoptosis and inhibit the proliferation of VSMCs by targetedly downregulating MMP‐9. [ 19 ] miR‐663 is found to be significantly reduced in VSMCs stimulated by platelet‐derived growth factor, and the miR‐663 overexpression not only enhances the expression of VSMCs differentiation marker genes such as smooth muscle 22α, but also effectively inhibits the proliferation and migration of VSMCs and alleviated intimal lesions. [ 20 ] In the present work, we confirmed that miR‐217 not only reduced the inflammatory response of VSMCs caused by HG, but also inhibited the proliferation and migration of VSMCs, and induced apoptosis of VSMCs.…”