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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01427

Bavachin protects human aortic smooth muscle cells against β-glycerophosphate-mediated vascular calcification and apoptosis via activation of mTOR-dependent autophagy and suppression of Wnt signaling

 Huqiang He1, 2, 3,  Betty Yuen Kwan Law2, 3, Ni Zhang2, 3,  Congling Qiu2, 3,  Yuanqing Qu2, 3, Anguo Wu4, 5,  YU HAN2, 3, Qi Song2, 3, 6, Wenlu Zheng2, 3, 7, 8, Yong Liu1, Yanzheng He1* and  Vincent Kam Wai Wong2, 3*
  • 1Department of Vascular Surgery, Affiliated Hospital of Southwest Medical University, China
  • 2State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, China
  • 3Faculty of Chinese Medicine, Macau University of Science and Technology, China
  • 4Department of Pharmacology, Southwest Medical University, China
  • 5Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Medicine, Southwestern Medical University, China
  • 6Affiliated Hospital of Southwest Medical University, China
  • 7Department of Nuclear Medicine, Affiliated Hospital, Southwest Medical University, China
  • 8Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China, China

Abstract
Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its underlying mechanism is still unclear. In this study, we aimed to identify the bioactive compounds from traditional Chinese medicines (TCM) that exhibit an anti-arteriosclerosis effect. In β-glycerophosphate (β-GP)-stimulated human aortic smooth muscle cells (HASMCs), the calcium level was increased and the expression of the calcification-related proteins OPG, OPN, Runx2, and BMP2 were all up-regulated, followed by autophagy induction and apoptosis. Meanwhile, we further revealed that β-GP induced apoptosis and promoted osteogenic differentiation of human osteoblastic cells via Wnt/β-Catenin signaling. Bavachin, a natural compound from Psoralea corylifolia, dose-dependently reduced the level of intracellular calcium and the expression of calcification-related proteins OPG, OPN, Runx2 and BMP2, thus inhibiting cell apoptosis. In addition, Bavachin increased LC3-II and beclin1 expression, along with intracellular LC3-II puncta formation, which autophagy induction is Atg7-dependent and is regulated by suppression of mTOR signaling. Furthermore, addition of autophagy inhibitor, wortmannin (WM) attenuated the inhibitory effect of Bavachin on β-GP-induced calcification and apoptosis in HASMCs. Collectively, the present study revealed that Bavachin protects HASMCs against apoptosis and calcification by activation of the Atg7/mTOR‐autophagy pathway and suppression of the Wnt/β-catenin signaling, our findings provide a potential clinical application for Bavachin in the therapy of cardiovascular disease.

Keywords: 血管钙化(VC), 自噬, 的Wnt /β-catenin的 , 细胞凋亡, ATG7

Received: 04 Mar 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 He, Law, Zhang, Qiu, Qu, Wu, HAN, Song, Zheng, Liu, He and Wong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Yanzheng He, Department of Vascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China, heyanzheng_2018@163.com
Dr. Vincent Kam Wai Wong, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China, bowaiwong@gmail.com