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

Journal Article · Sat Dec 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.10.198· OSTI ID:23125089

Han, Hao ^[1]; Yang, Shu ^[2]; Liang, Yu ^[1]; Zeng, Peng; Liu, Lipei ^[2]; Yang, Xiaoxiao; Duan, Yajun ^[1]; Han, Jihong ^[1]; Chen, Yuanli ^[1]

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1. School of Food and Biological Engineering, Hefei University of Technology, Hefei (China)
2. College of Life Sciences, Key Laboratory of Bioactive Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin (China)

Highlights: • Teniposide induces expression of VSMC contractile markers in aortic lesion plaques and HASMCs. • Teniposide inhibits VSMC phenotype switching by inducing miR-21 expression. • Teniposide ameliorates ligation-induced carotid artery remodeling in C57BL/6J mice. • The anti-vascular remodeling effect of teniposide suggests the potential application of Topo II inhibitors on occlusive vascular diseases. 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.

• OSTI ID: 23125089
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 506; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

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