Int J Biol Sci 2017; 13(8):1067-1081. doi:10.7150/ijbs.20316
Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol
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.
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
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