PCSK9——高胆固醇血症的新靶点

PCSK9——New Target of Hypercholesterolemia

前蛋白转化酶枯草溶菌素9基因(PCSK9)是近十年来发现的一种新的致病基因,基因突变主要有功能获得型、功能缺失型,前者通过介导肝脏低密度脂蛋白受体(LDLR)的降解、减少LDLR的数量、降低肝脏对LDLR的清除,引起高胆固醇血症,在脂质代谢中发挥着重要作用。血清中低密度脂蛋白胆固醇(LDL-C)水平与冠心病的发生风险呈正相关,使用他汀类等降脂药物后,大大降低了高胆固醇血症患者的LDL-C及冠心病的发病风险,但仍有大部分患者LDL-C未达到理想目标。动物实验及临床试验显示,PCSK9抑制剂可大幅度降低各种高胆固醇患者的LDL-C水平,给高胆固醇血症患者带来了福音;但其发挥作用的确切机制需进一步研究。

Proprotein convertase subtilisin / kexin 9 gene（ PCSK9） is a new pathogenic gene discovered over the past decade,and there are mainly two gene mutations： gaining function,losing function,the former regulates liver low-density lipoprotein receptor（ LDLR） degradation,to reduce the level of LDLR,and the reduced hepatic clearance of LDLR,causes hypercholesterolemia,which plays an important role in lipid metabolism. Serum low-density lipoprotein cholesterol（ LDL-C） concentration and the risk of coronary heart disease are positively correlated,and the use of statins and other lipid-lowering drugs,greatly reduce the level of LDL-C and the risk of coronary heart disease in hypercholesterolemia,though the majority of patients do not achieve the desired LDL-C goal. Animal experiments and clinical trials show that PCSK9 inhibitors can significantly reduce LDL-C concentrations in patients with hypercholesterolemia,benefitting the patients,though the exact mechanism needs further studies.