miR‑155 induces endothelial cell apoptosis and inflammatory response in atherosclerosis by regulating Bmal1

Abstract

Atherosclerosis is the leading cause of death from vascular diseases worldwide, and endothelial cell (EC) dysfunction is the key cause of atherosclerosis. <i>miR-155</i> was found to induce endothelial injury and to trigger atherosclerosis. In addition, brain and muscle ARNT-like protein-1 (Bmal1) has been found to be closely related to EC function. Therefore, the present study aimed to explore the mechanism underlying the regulation of Bmal1 by <i>miR-155</i> in the induction of EC apoptosis and inflammatory response in atherosclerosis. The atherosclerosis model in apolipoprotein E (ApoE)^- ^/ ^- mice was established. <i>miR-155</i> and Bmal1 expression was quantified by RT-qPCR and western blot analysis, respectively. The role of <i>miR-155</i> and Bmal1 in atherosclerosis was evaluated through changes in cardiac function, plaque area, cardiomyocyte apoptosis, and inflammatory factor levels in mice. Moreover, the regulatory relationship between them was identified by dual-luciferase reporter gene assay to explore the mechanism of action of <i>miR-155</i>. After the modeling, the expression of <i>miR-155</i> was upregulated and Bmal1 was downregulated in aorta, and there was a significant linear correlation between them. Upregulation of <i>miR-155</i> increased the atherosclerotic plaque area, cell apoptosis, total cholesterol (TC) and triglyceride (TG), as well as weakened aortic diastolic function. However, opposite changes occurred after downregulation of <i>miR-155</i> or an increase in Bmal1. In addition, the microRNA.org website predicted that there were targeted binding sites between <i>miR-155</i> and Bmal1, which was verified with a dual-luciferase reporter gene assay. <i>miR-155</i> was able to inhibit the expression by targeting Bmal1. Moreover, a rescue experiment showed that Bmal1 hindered the promotion of <i>miR-155</i> in regards to atherosclerosis. In conclusion, <i>miR-155</i> induces EC apoptosis and inflammatory response, weakens aortic diastolic function, and promotes the progression of atherosclerosis through targeted inhibition of Bmal1.