Affiliations: [a]
Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| [b]
Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| [c]
Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
Correspondence:
[*]
Corresponding author: Xiao-Lan Wei, Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China. E-mail: weixiaolan198306@163.com
Abstract: OBJECTIVE:Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS:
In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100μg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS:The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION:Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.
