Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling

Hu-Qiang He; Betty Yuen Kwan Law; Ni Zhang; Cong-Ling Qiu; Yuan-Qing Qu; An-Guo Wu; Yu Han; Qi Song; Wen-Lu Zheng; Yong Liu; Yan-Zheng He; Vincent Kam Wai Wong

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 β-Catenin Signaling

Front Pharmacol. 2019 Dec 19:10:1427. doi: 10.3389/fphar.2019.01427. eCollection 2019.

Authors

Hu-Qiang He^{1

2

3}, Betty Yuen Kwan Law^{1

2}, Ni Zhang^{1

2}, Cong-Ling Qiu^{1

2}, Yuan-Qing Qu^{1

2}, An-Guo Wu^{4

5}, Yu Han^{1

2}, Qi Song^{1

2

6}, Wen-Lu Zheng^{1

2

7

8}, Yong Liu³, Yan-Zheng He³, Vincent Kam Wai Wong^{1

2}

Affiliations

¹ Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.
² State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
³ Department of Vascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁴ Department of Thoracic and Cardial Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁵ Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁶ Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁷ Laboratory of Chinese Materia Medical, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
⁸ Institute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Southwest Medical University, Luzhou, 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 pathogenic mechanism is far from clear. Here, 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 of human osteoblasts and promoted differentiation of osteoblasts through 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 β-catenin signaling, our findings provide a potential clinical application for bavachin in the therapy of cardiovascular disease.

Keywords: Apoptosis; Atg7; Wnt/β-catenin; autophagy; vascular calcification.