AUTHOR=Hu Wangming , Wu Xiao , Jin Zhong , Wang Zheng , Guo Qiru , Chen Zixian , Zhu Song , Zhang Haidi , Huo Jian , Zhang Lingling , Zhou Xin , Yang Lan , Xu Huan , Shi Liangqing , Wang Yong 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.783872

DOI=10.3389/fcvm.2021.783872

ISSN=2297-055X

ABSTRACT=Abstract
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 that how to regulate SMC phenotypic switching is still need to be defined. This study aims to investigate the effect of Andrographolide on pathological vascular remodeling and its underlying mechanism.
Methods
C57/BL6 mouse left carotid artery complete ligation model and rat SMC were used to determine whether Andrographolide is critical in regulating SMC phenotypic switching. Quantitative real-time PCR, CCK8 cell proliferation assay, BRDU incorporation assay, Boyden chamber migration assay and Spheroid sprouting assay were performed to evaluate whether Andrographolide suppresses proliferation and migration of SMC. Immunohistochemistry staining, Immunofluorescence staining and protein CO-immunoprecipitation were used to observe interaction between EDNRA, EDNRB and Myocardin-SRF.
Results
Andrographolide inhibits neointimal hyperplasia in left carotid artery complete ligation model. Andrographolide regulates SMC phenotypic switching characterized by suppressing proliferation and migration of SMC. Andrographolide activities Endothelin signaling pathway exhibited by dramatically inducing EDNRA and EDNRB expression. The interaction between EDNRA/EDNRB and Myocardin-SRF resulting in promoting SMC differentiation marker genes expression.
Conclusion
Andrographolide plays a critical role in regulating pathological vascular remodeling.