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

Liang,Shuangchao; Hu,Jiqiong; Zhang,Andong; Li,Fangkuan; Li,Xiaoqiang

doi:10.3892/etm.2020.9259

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

Authors:
- Shuangchao Liang
- Jiqiong Hu
- Andong Zhang
- Fangkuan Li
- Xiaoqiang Li
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Affiliations: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Department of Vascular Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241000, P.R. China
Published online on: October 1, 2020 https://doi.org/10.3892/etm.2020.9259
Article Number: 128
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis is the leading cause of death from vascular diseases worldwide, and endothelial cell (EC) dysfunction is the key cause of atherosclerosis. miR‑155 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 miR‑155 in the induction of EC apoptosis and inflammatory response in atherosclerosis. The atherosclerosis model in apolipoprotein E (ApoE)^‑/‑ mice was established. miR‑155 and Bmal1 expression was quantified by RT‑qPCR and western blot analysis, respectively. The role of miR‑155 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 miR‑155. After the modeling, the expression of miR‑155 was upregulated and Bmal1 was downregulated in aorta, and there was a significant linear correlation between them. Upregulation of miR‑155 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 miR‑155 or an increase in Bmal1. In addition, the microRNA.org website predicted that there were targeted binding sites between miR‑155 and Bmal1, which was verified with a dual‑luciferase reporter gene assay. miR‑155 was able to inhibit the expression by targeting Bmal1. Moreover, a rescue experiment showed that Bmal1 hindered the promotion of miR‑155 in regards to atherosclerosis. In conclusion, miR‑155 induces EC apoptosis and inflammatory response, weakens aortic diastolic function, and promotes the progression of atherosclerosis through targeted inhibition of Bmal1.

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