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Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and β-catenin signaling pathways

ZHONG Hui¹, LI Dai-Ying², WANG Su-Ying², CHEN Jie-Yi², CHEN Jia-Xin¹, TAN Xiao¹, WANG Yue-Heng¹, XIE Yu-Chen¹, ZHU Dong-Xing^1,*

¹Biomedical Research Center, Basic Medical School, Guangzhou Medical University, Guangzhou 511436, China；²School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China

Abstract

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and β-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and β-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and β-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.

Key words: Tanshinone IIa; vascular calcification; vascular smooth muscle cells; NF-κB and β-catenin signaling pathways

Received: 　　Accepted:

Corresponding author: 朱东兴　　E-mail: dongxing.zhu@gzhmu.edu.cn

Citing This Article：

ZHONG Hui, LI Dai-Ying, WANG Su-Ying, CHEN Jie-Yi, CHEN Jia-Xin, TAN Xiao, WANG Yue-Heng, XIE Yu-Chen, ZHU Dong-Xing. Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and β-catenin signaling pathways. Acta Physiol Sin 2022; 74 (6): 949-958 (in Chinese with English abstract).