Maligłówka Mateusz, Kosowski Michał, Hachuła Marcin, Cyrnek Marcin, Bułdak Łukasz, Basiak Marcin, Bołdys Aleksandra, Machnik Grzegorz, Bułdak Rafał Jakub, Okopień Bogusław
Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, Poland.
Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland.
Metabolites. 2022 Mar 17;12(3):256. doi: 10.3390/metabo12030256.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (e.g., alirocumab, evolocumab) in decreasing cardiovascular risk, pleiotropic effects of other lipid-lowering drugs (e.g., statins) and the multifunctional character of other proprotein convertases, were the cause for proceeding studies on functions of PCSK9 beyond cholesterol metabolism. In this article, we summarize the current knowledge on the roles that PCSK9 plays in different tissues and perspectives for its clinical use.
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）是前蛋白转化酶（PCs）家族中最后发现的成员，主要在肝细胞中合成。这种丝氨酸蛋白酶在减少肝细胞表面低密度脂蛋白受体（LDLR）数量方面起关键作用，这会导致血液中胆固醇水平升高。这种机制以及PCSK9功能获得（GOF）突变会导致家族性高胆固醇血症，而功能丧失（LOF）突变与低胆固醇血症相关这一事实，促使了阻断PCSK9作用的药物的发明。PCSK9抑制剂（如阿利西尤单抗、依洛尤单抗）在降低心血管风险方面的高效性、其他降脂药物（如他汀类药物）的多效性作用以及其他前蛋白转化酶的多功能特性，是开展PCSK9在胆固醇代谢以外功能研究的原因。在本文中，我们总结了目前关于PCSK9在不同组织中作用的知识及其临床应用前景。
