Li Wei-Wei, Guo Ze-Ming, Wang Bing-Cai, Liu Qing-Quan, Zhao Wen-An, Wei Xiao-Lan
Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Clin Hemorheol Microcirc. 2025;89(1):55-67. doi: 10.3233/CH-242172.
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.
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.
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.
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.
动脉粥样硬化是一种慢性动脉炎症性疾病，其发病机制与内皮功能障碍有关。研究发现，枯草杆菌蛋白酶/kexin9型蛋白转化酶（PCSK9）在动脉粥样硬化中起重要作用，但其具体机制仍不清楚。
在本研究中，我们首先用50或100μg/ml氧化低密度脂蛋白（ox-LDL）培养人脐静脉内皮细胞（HUVECs）24小时，以建立冠状动脉粥样硬化细胞模型。
结果表明，ox-LDL以浓度依赖的方式诱导HUVEC损伤和自噬，并上调HUVECs中PCSK9蛋白表达。用siRNA沉默PCSK9表达可抑制ox-LDL诱导的HUVEC内皮功能障碍，抑制炎症因子释放，促进HUVEC增殖并抑制凋亡。此外，ox-LDL增加了LC3B-I和LC3B-II的表达，降低了p62的表达。然而，这些过程被sh-PCSK9逆转。此外，sh-PCSK9可抑制PI3K、AKT和mTOR磷酸化并促进自噬。
综上所述，我们的研究表明，沉默PCSK9可抑制PI3K/ATK/mTOR通路，激活ox-LDL诱导的血管内皮细胞自噬，减轻内皮细胞损伤和炎症。
