Activation of Nrf2 attenuates pulmonary vascular remodeling via inhibiting endothelial-to-mesenchymal transition
- Author:
Yu-Cai CHEN
1
;
Tian-Yi YUAN
;
Di CHEN
;
Lian-Hua FANG
;
Yang LYU
;
Guan-Hua DU
Author Information
1. Beijing Key Laboratory of Drug Targets Identification and Drug Screening
- Keywords:
Salvianolic acid A;
endothelial-to-mesenchymal transition;
TGF-β1;
Nrf2;
pulmonary ar?terial hypertension;
antioxidant
- From:
Chinese Journal of Pharmacology and Toxicology
2018;32(4):275-276
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the pharmacological effect and mechanism of Salvianolic acid A (SAA) on pulmonary vascular remodeling. METHODS In current study, we conducted a series of experiments to clarify the effect of SAA,a kind of polyphenol compound,in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was also induced by TGF-β1in human pulmonary arterial endothelial cells(HPAECs) in vitro.RESULTS SAA significantly attenuated EndMT,simul-taneously inhibited cell migration and reactive oxygen species(ROS)formation.In MCT-induced pulmonary arterial hypertension(PAH)model,SAA improved vascular function,decreased TGF-β1level and inhib-ited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygen-ase-1(HO-1)up-regulation.The effect of SAA on EndMT in vitro was abolished by ZnPP,a HO-1 inhibitor. CONCLUSION This study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.
