Department of Neurology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
J Immunol Res. 2020 Oct 14;2020:2687692. doi: 10.1155/2020/2687692. eCollection 2020.
Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is often upregulated in the presence of sepsis and infectious diseases. In sepsis, PCSK9 degraded the low-density lipoprotein cholesterol (LDL) receptors (LDL-R) of the hepatocytes and the very low-density lipoprotein cholesterol receptors (VLDL-R) of the adipocytes, which then subsequently reduced pathogenic lipid uptake and clearance/sequestration. Moreover, it might improve cholesterol accumulation and augment toll-like receptor function in macrophages, which supported inflammatory responses. Accordingly, PCSK9 might show detrimental effects on immune host response and survival in sepsis. However, the exact roles of PCSK9 in the pathogenesis of sepsis are still not well defined. In this review, we summarized the literatures focusing on the roles of PCSK9 in sepsis. Our review provided an additional insight in the role of PCSK9 in sepsis, which might serve as a potential target for the treatment of sepsis.
脓毒症是一种危及生命的器官功能障碍综合征，由宿主对感染的失调反应引起。在脓毒症和感染性疾病存在的情况下，前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）通常会被上调。在脓毒症中，PCSK9 降解了肝细胞的低密度脂蛋白胆固醇（LDL）受体（LDL-R）和脂肪细胞的极低密度脂蛋白胆固醇受体（VLDL-R），随后减少了致病脂质的摄取和清除/隔离。此外，它可能会增加巨噬细胞中的胆固醇积累并增强 Toll 样受体功能，从而支持炎症反应。因此，PCSK9 可能对脓毒症中的免疫宿主反应和存活产生有害影响。然而，PCSK9 在脓毒症发病机制中的确切作用仍未得到很好的定义。在这篇综述中，我们总结了专注于 PCSK9 在脓毒症中作用的文献。我们的综述为 PCSK9 在脓毒症中的作用提供了新的认识，这可能成为脓毒症治疗的潜在靶点。
