MicroRNA-217 is involved in the progression of atherosclerosis through regulating inflammatory responses by targeting sirtuin 1

Abstract

Atherosclerosis is a chronic inflammatory disease, and it is a global clinical problem. The development of new and effective therapeutic targets for atherosclerosis is necessary. A number of microRNAs (miRNAs) have been demonstrated to serve a crucial role in atherosclerosis. However, the role of miRNA (miR)-217 in atherosclerosis remains unclear. Therefore, the aim of the present study was to investigate the role and mechanism of miR-217 in atherosclerosis. The level of miR-217 was detected in the blood of patients with atherosclerosis using reverse transcription-quantitative PCR. THP-1 acute monocytic leukemia cells were treated with oxidized low-density lipoprotein (ox-LDL) to develop an atherosclerotic cell model of macrophages. The relationship between miR-217 and sirtuin 1 (SIRT1) was determined by TargetScan and dual luciferase reporter assay. Cell apoptosis was measured by flow cytometry. Production of pro-inflammatory factors and triglyceride (TG) and total cholesterol (TC) levels were also determined. The results demonstrated that miR-217 was significantly upregulated in atherosclerosis. SIRT1 was demonstrated to be a direct target of miR-217 and was downregulated in atherosclerosis. Downregulation of miR-217 significantly inhibited ox-LDL-induced TG and TC level increase, cell apoptosis and the upregulation of the pro-inflammatory factors tumor necrosis factor a, interleukin (IL)-6 and IL-1β. Additionally, the SIRT1/AMP-activated protein kinase α/NF-κB pathway was at least partially involved in modulating the effects of miR-217 inhibition on THP-1 cells treated with ox-LDL. In addition, the effects of miR-217 downregulation on ox-LDL-treated THP-1 cells were eliminated by SIRT1 silencing. In conclusion, the results of the present study indicated that miR-217 downregulation may relieve atherosclerosis through the inhibition of macrophage apoptosis and inflammatory response by targeting SIRT1.