Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling

作者：Wangming Hu, Xiao Wu, Zhong Jin, Zheng Wang, Qiru Guo, Zixian Chen, Song Zhu, Haidi Zhang, Jian Huo, Lingling Zhang, Xin Zhou, Lan Yang, Huan Xu, Liangqing Shi, Yong Wang · 发表于：Frontiers in Cardiovascular Medicine · 年份：2022 · DOI：10.3389/fcvm.2021.783872 · 被引用次数：14 · 研究领域：Andrographolide Research and Applications、Phytochemicals and Medicinal Plants、Phytochemistry and biological activities of Ficus species

INTRODUCTION: Pathological vascular remodeling is a hallmark of various vascular diseases. Smooth muscle cell (SMC) phenotypic switching plays a pivotal role during pathological vascular remodeling. The mechanism of how to regulate SMC phenotypic switching still needs to be defined. This study aims to investigate the effect of Andrographolide, a key principle isolated from Andrographis paniculate, on pathological vascular remodeling and its underlying mechanism. METHODS: A C57/BL6 mouse left carotid artery complete ligation model and rat SMCs were used to determine whether Andrographolide is critical in regulating SMC phenotypic switching. Quantitative real-time PCR, a CCK8 cell proliferation assay, BRDU incorporation assay, Boyden chamber migration assay, and spheroid sprouting assay were performed to evaluate whether Andrographolide suppresses SMC proliferation and migration. Immunohistochemistry staining, immunofluorescence staining, and protein co-immunoprecipitation were used to observe the interaction between EDNRA, EDNRB, and Myocardin-SRF. RESULTS: Andrographolide inhibits neointimal hyperplasia in the left carotid artery complete ligation model. Andrographolide regulates SMC phenotypic switching characterized by suppressing proliferation and migration. Andrographolide activates the endothelin signaling pathway exhibited by dramatically inducing EDNRA and EDNRB expression. The interaction between EDNRA/EDNRB and Myocardin-SRF resulted in promoting SMC differentiation ...