microRNA-181a is upregulated in human atherosclerosis plaques and involves in the oxidative stress-induced endothelial cell dysfunction through direct targeting Bcl-2

G. Liu, Y. Li, X.-G. Gao

Department of Internal Medicine, Tianjin Huanhu Hospital, Hexi District, Tianjin, China. gangliuhhh@163.com

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• Metabolism

OBJECTIVE: Atherosclerosis is featured as artery wall thickness as a result of invasion and accumulation of white blood cells and proliferation of intimal smooth muscle cells. Endothelial dysfunction has been linked to a variety of vascular diseases, including atherosclerosis. MicroRNAs play essential roles during the atherosclerotic plaques formation. In this study, we investigate the roles of miR-181a in the oxidative stress-induced endothelial cells dysfunction.

MATERIALS AND METHODS: The expressions of miR-181a were compared between human atherosclerotic plaques and normal blood vessels. The Bcl-2 protein expression was measured by Western blot and mRNA expression was measured by qRT-PCR. HUVECs were transiently transfected with pre-miR-181a or control microRNAs by Lipofectamine 2000. The viability of HUVECs in response to H2O2 was measured by MTT assay.

RESULTS: We report miR-181a is upregulated in human atherosclerotic plaques compared with the normal blood vessel. The miR-181a is induced by H2O2 treatments. The exogenous overexpression of miR-181a accelerates the apoptosis rates of HUVECs in response to H2O2. We identify Bcl-2 as a direct target of miR-181a. Also, we observed H2O2 treatments inhibited Bcl-2 expressions at both protein and mRNA levels. Inhibition of miR-181a restores Bcl-2 expressions, leading to increased resistance to H2O2. Moreover, restoration of Bcl-2 in miR-181a-overexpressing HUVECs renders cells tolerate higher concentrations of H2O2. Finally, a reverse correlation between miR-181a and Bcl-2 expression in human atherosclerosis plaques is illustrated.

CONCLUSIONS: Our results revealed an essential role of miR-181a in the development of atherosclerosis through the regulation of the endothelial dysfunction, providing mechanisms for the development of new antioxidant drugs for the treatment of atherosclerosis.

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