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Teniposide regulates the phenotype switching of vascular smooth muscle cells in a miR-21-dependent manner

Author:
Han, Hao, Yang, Shu, Liang, Yu, Zeng, Peng, Liu, Lipei, Yang, Xiaoxiao, Duan, Yajun, Han, Jihong, Chen, Yuanli
Source:
Biochemical and biophysical research communications 2018 v.506 no.4 pp. 1040-1046
ISSN:
0006-291X
Subject:
DNA topoisomerase (ATP-hydrolysing), actin, atherosclerosis, calcification, carotid arteries, gene expression regulation, genes, humans, mice, muscle protein, myocytes, osteopontin, phenotype, platelet-derived growth factor, smooth muscle
Abstract:
The switch of vascular smooth muscle cells (SMCs) from the contractile phenotype to proliferative one can make contributions to atherosclerosis and neointima formation. MiR-21 can prevent the rupture of advanced lesion plaques. We previously reported the protection of DNA topoisomerase II (Topo II) inhibitors against atherosclerosis and vascular calcification. However, it remains unknown if Topo II inhibitors can change SMC phenotypes. Herein, we show that teniposide protected SMC phenotype switching during atherosclerosis by enhancing expression of smooth muscle α-actin (SMA) while reducing osteopontin (OPN) expression in aortic lesion plaques. In vitro, teniposide induced expression of smooth muscle protein 22-α and calponin 1, but inhibited expression of OPN and epiregulin in human aortic SMCs (HASMCs). Moreover, teniposide attenuated platelet derived growth factor-BB-induced HASMC proliferation and migration. Mechanistically, the effect of teniposide on SMC phenotypes was completed, at least in part, by activating miR-21 expression. In addition, teniposide ameliorated ligation-induced carotid artery remodeling in C57BL/6J mice by regulating SMA and OPN expression. Taken together, our study demonstrates that teniposide regulates SMC phenotype switching by upregulating expression of contractile genes in a miR-21-dependent manner, and this function is an important anti-atherogenic mechanism of teniposide.
Agid:
6225450