Paeonol alleviated ox-LDL-induced HUVEC injury by regulating the PI3K/AKT pathway via targeting HMOX1. - GreenMedInfo Summary

Atherosclerosis is a leading cause of vascular disease worldwide. Paeonol has been reported to have therapeutical potential in atherosclerosis. The aim of this study is to explore the effect of paeonol on oxidized low-density lipoprotein (ox-LDL)-induced endothelial cells injury and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (100 μg/ml) to mimic atherosclerosis in vitro. The cell viability, proliferation, and apoptosis were assessed by cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, respectively. The angiogenesis was detected by tube formation assay. The levels of inflammatory factor were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the levels of Fe, reactive oxygen species (ROS), and glutathione (GSH) were detected to assess ferroptosis. The western blot was used to detect the protein expression. Ox-LDL inhibited cell viability, proliferation, and angiogenesis, but induced apoptosis and inflammation in HUVECs, and paeonol (75 μM) relieves ox-LDL-induced HUVEC injury. Also, paeonol inhibited ox-LDL-induced ferroptosis of HUVECs. Interestingly, heme oxygenase-1 (HMOX1) knockdown alleviated ox-LDL-induced HUVECs injury and ferroptosis. Paeonol affected ox-LDL-induced HUVECs via regulating HMOX1. In addition, paeonol regulated PI3K/AKT pathway via HMOX1, and the inhibitor of phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway reversed the effects of HMOX1 knockdown on ox-LDL-induced HUVECs. Paeonol alleviated ox-LDL-induced HUVEC injury by regulating the PI3K/AKT pathway via targeting HMOX1.