Salvianolic acid A reduces endothelial-mesenchymal transition of HPAECs

OBJECTIVE Salvianolic acid A(SAA), a polyphenols acid, is a bioactive ingredient from a traditional Chinese medicine named Danshen(Salvia Miltiorrhiza Bunge). According to previous studies, it was shown to possess various effects such as anti-oxidative stress, anti-diabetic complications and anti-pulmonary hypertension. This study is aimed to investigate the effect of SAA on pulmonary arterial endothelial-mesenchymal transition(endo MT) induced by hypoxia and the underlying mechanisms. METHODS Primary cultured human pulmonary arterial endothelial cells(HPAECs)were exposed to 1% O2 for 48 h with or without SAA treatment. RESULTS SAA treatment improved the morphology of HPAECs and inhibited the cytoskeleton remodeling and reduced migration distances. 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 α-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. CONCLUSION SAA treatment can protect HPAECs from endo MT induced by hypoxia, which may perform via the downstream effectors of BMPRs or TGFβR including Smads, ERK and ROCK/cofilin pathways.