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.Free PDF Download
To cite this article
G. Liu, Y. Li, X.-G. Gao
microRNA-181a is upregulated in human atherosclerosis plaques and involves in the oxidative stress-induced endothelial cell dysfunction through direct targeting Bcl-2
Eur Rev Med Pharmacol Sci
Vol. 20 - N. 14