Vaccarin prevents ox-LDL-induced HUVEC EndMT, inflammation and apoptosis by suppressing ROS/p38 MAPK signaling

Am J Transl Res. 2019 Apr 15;11(4):2140-2154. eCollection 2019.


Oxidized low-density lipoprotein (ox-LDL)-induced endothelial-mesenchymal transition (EndMT), inflammation and apoptosis in endothelial cells play crucial roles in the progression of cardiovascular diseases including atherosclerosis. Vaccarin is a flavonoid glycoside from vaccariae semen associated with powerful cardiovascular protective effects. However, the effects of vaccarin on human umbilical vein endothelial cells (HUVEC) injury in response to ox-LDL remain unknown. Herein, we showed that treatment with vaccarin significantly suppressed ox-LDL-induced HUVEC inflammation, EndMT and apoptosis. Mechanistically, the HUVECs exposed to ox-LDL exhibited enlarged reactive oxygen species (ROS) production and p38 MAPK phosphorylation, which was counteracted by vaccarin. Importantly, ROS activator hydrogen peroxide (H2O2) and p38 MAPK activator anisomycin pretreatment prevent the protective effect of vaccarin on endothelial injury induced by ox-LDL. Our study suggested that vaccarin impeded ox-LDL-triggered HUVEC inflammation, EndMT and apoptosis via inhibition of ROS/p38 MAPK signaling pathway. Vaccarin may have a therapeutic effect on endothelial injury-related disorders.

Keywords: EndMT; HUVECs; apoptosis; inflammation; ox-LDL; vaccarin.