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