Inhibition of vascular calcification by Compound Danshen Dripping Pill through multiple mechanisms

作者：Yanfang Yang, Liying Yuan, Hui Xiong, Kaimin Guo, Mengying Zhang, Tengteng Yan, Wenjia Wang, Shuiping Zhou, He Sun, Shuang Zhang, Yajun Duan, Yunhui Hu · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.155618 · 被引用次数：11 · 研究领域：Traditional Chinese Medicine Analysis、Ginseng Biological Effects and Applications、Lipid metabolism and disorders

BACKGROUND: Vascular calcification refers to the abnormal accumulation of calcium in the walls of blood vessels and is a risk factor often overlooked in cardiovascular disease. However, there is currently no specific drug for treating vascular calcification. Compound Danshen Dripping Pill (CDDP) is widely used to treat cardiovascular diseases, but its effect on vascular calcification has not been reported. PURPOSE: mice and in vitro and elucidated its mechanism of action. STUDY DESIGN: mice were fed a high-fat diet randomly supplemented with CDDP for 16 weeks. Atherosclerosis and vascular calcification were determined. In vitro, human aortic smooth muscle cells (HASMCs), human umbilical vein endothelial cells (HUVECs), and human aortic endothelial cells (HAECs) were used to determine the mechanisms for CDDP-inhibited vascular calcification. RESULTS: In this study, we observed that CDDP reduced intimal calcification in atherosclerotic lesions of ApoE-deficient mice fed a high-fat diet, as well as the calcification in cultured SMCs and ECs. Mechanistically, CDDP inhibited the Wnt/β-catenin pathway by up-regulating the expression of DKK1 and LRP6, which are upstream inhibitors of Wnt, leading to a reduction in the expression of osteoblastic transition markers (ALP, OPN, BMP2, and RUNX2). Furthermore, CDDP enhanced the secretion of DKK1, which plays a role in mediating EC-SMC crosstalk in calcification. Additionally, VC contributes to vascular aging by inhibiting Sirt1 and increa...