Effect of Salvianolic acid A on the endothelial-mesenchymal transition of HPAECs induced by hypoxia

[Speaker] Lian-Hua Fang:1
[Co-author] Tian-Yi Yuan:1, Yu-Cai Chen:1, Li Zhang:2, Yang Lyu:2, Guan-Hua Du:1
1:Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, China, 2:Beijing Key Laboratory of Polymorphic Drugs, China

Background: Salvianolic acid A (SAA) is a bioactive ingredient from a traditional Chinese medicine called Dan Shen (Salvia Miltiorrhiza Bunge). Previous study was shown to have various effects such as anti-oxidative stress, antidiabetic complications and anti-pulmonary hypertension. Objective: This study aimed to investigate the effect of SAA on pulmonary arterial endothelial-mesenchymal transition (EndoMT) induced by hypoxia and the underlying mechanisms. Methods: Human pulmonary arterial endothelial cells (HPAECs) were exposed to 1% O2 for 24 h and 48 h with or without SAA treatment. Results: SAA treatment improved the morphology of HPAECs and inhibited the cytoskeleton remodeling. 3 microM SAA reduced migration distances from 262.2 micro-meter to 198.4 micro-meter at 24 h and 344.8 micro-meter to 109.3 micro-meter at 48 h. It was observed that the production of ROS in cells was significantly reduced by the treatment of SAA. Meanwhile, SAA alleviated the loss of CD31 and slightly inhibited the expression of alpha-SMA. The mechanisms study shows that SAA treatment increased the phosphorylation levels of Smad1/5, but inhibited that of Smad2/3. Furthermore, SAA attenuated the phosphorylation levels of ERK and Cofilin, which were enhanced by hypoxia. Conclusions: This study indicated that SAA treatment can protect HPAECs from endoMT induced by hypoxia, which may perform via the inhibition on ROS production and further through the downstream effectors of BMPRs or TGF-betaR including Smads, ERK and ROCK/cofilin pathways.
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Acknowledgements: This work was supported by grants from the National Natural Science Foundation of China (81773935, 81573645, 81603101) and CAMS Innovation Fund for Medical Sciences (2017-I2M-1-010).

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