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Int J Biol Sci 2017; 13(8):1067-1081. doi:10.7150/ijbs.20316

Research Paper

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

Yucai Chen1, Tianyi Yuan1,2, Huifang Zhang1, Yu Yan1, Danshu Wang1, Lianhua Fang1✉, Yang Lu3, Guanhua Du2✉

1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines;
2. Beijing Key Laboratory of Drug Targets Identification and Drug Screening;
3. Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Abstract

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (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 induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In 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.

Keywords: salvianolic acid A, endothelial-to-mesenchymal transition, TGFβ1, Nrf2, pulmonary arterial hypertension, antioxidant

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How to cite this article:
Chen Y, Yuan T, Zhang H, Yan Y, Wang D, Fang L, Lu Y, Du G. Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol. Int J Biol Sci 2017; 13(8):1067-1081. doi:10.7150/ijbs.20316. Available from http://www.ijbs.com/v13p1067.htm