PP2A alleviates oxidized LDL-induced endothelial dysfunction by regulating LOX-1/ROS/MAPK axis

Abstract

AimsThe purpose of this study is to investigate the effect of PP2A on the progression of AS and the special molecular mechanism. Main methodsThe expression of PP2A in Human umbilical vein endothelial cells (HUVECs) induced by different concentrations of Ox-LDL was measured by RT-PCR and Western blot. The binding activity of PP2A and LOX-1 was determined by CoIP assay. Western blot was used to measure the protein expression of VCAM-1, ICAM-1 and MCP-1. Key findingThe results revealed that the expression of PP2A was decreased with the increase of Ox-LDL concentration in HUVECs. Overexpression of PP2A alleviated Ox-LDL-induced dysfunction and inflammatory response in HUVECs. The results of Co-immunoprecipitation (CoIP) showed that PP2A had direct effect on LOX-1, and PP2A inhibited the expression of LOX-1. In addition, overexpression of LOX-1 reversed the inhibitory effect of PP2A on Ox-LDL-induced dysfunction and inflammatory response in HUVECs. What is more, PP2A inhibited LOX-1/ROS/MAPK axis. Significanceit suggests that PP2A alleviates Ox-LDL-induced dysfunction and inflammatory response of HUVECs potentially by regulating the LOX-1/ROS/MAPK axis，which suggests that PP2A has anti-inflammatory effect during the formation of as, and the molecular therapy of PP2A provides a theoretical basis.