1. Academic Validation
  2. Salvianolic acid B inhibits Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression

Salvianolic acid B inhibits Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression

  • Phytomedicine. 2019 May;58:152754. doi: 10.1016/j.phymed.2018.11.014.
Xue-Shan Zhao 1 Bin Zheng 1 Ya Wen 2 Yan Sun 1 Jin-Kun Wen 3 Xin-Hua Zhang 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
  • 2 Department of Neurology, the Second Hospital of Hebei Medical University, Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, China.
  • 3 Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: wjk@hebmu.edu.cn.
  • 4 Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: xiaomifeng800815@126.com.
Abstract

Background: Salvianolic acid B (Sal B), a water-soluble compound extracted from Salvia miltiorrhiza that has been widely used to treat cardiovascular diseases for hundreds of years in China, exerts cardiovascular protection by multiple mechanisms. miR-146a is involved in vascular smooth muscle cell (VSMC) phenotypic modulation and proliferation. However, it has yet to be investigated whether the cardiovascular protective effect of Sal B is mediated by miR-146a.

Purpose: To determine the relationship among the cardiovascular protective effect of Sal B, miR-146a expression, and VSMC proliferation.

Methods: MTS assay and cell counting were performed to evaluate the effect of Ang II, Sal B and miR-146a on VSMC proliferation. The neointima hyperplasia was assessed by hematoxylin/eosin staining. qRT-PCR was used to detect the expression of miR-146a, KLF5, cyclin D1 and PCNA. Western blot analysis was used to detect the expressions of KLF5, cyclin D1 and PCNA after miR-20b-5p was knocked down or overexpressed in VSMC.

Results: Sal B suppressed intimal hyperplasia induced by carotid artery ligation and decreased Ang II-induced VSMC proliferation by down-regulating the positive cell-cycle regulators KLF5 and cyclin D1. Further experiments showed that VSMC proliferation and upregulation of KLF5 and cyclin D1 induced by Ang II were accompanied by elevated miR-146a level. Furthermore, overexpression of miR-146a promoted and knockdown of miR-146a reduced Ang II-induced VSMC proliferation and ameliorated intimal hyperplasia induced by carotid artery ligation. Sal B inhibited Ang II-induced VSMC proliferation by suppressing miR-146a expression.

Conclusion: Sal B inhibited Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression.

Keywords

KLF5; Proliferation; Salvianolic acid B; VSMC; miR-146a.

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