Péč Martin Jozef, Benko Jakub, Jurica Jakub, Péčová Monika, Samec Marek, Hurtová Tatiana, Bolek Tomáš, Galajda Peter, Péč Martin, Samoš Matej, Mokáň Marián
Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia.
Department of Cardiology, Teaching Hospital Nitra, 949 01 Nitra, Slovakia.
Pharmaceuticals (Basel). 2023 Aug 22;16(9):1197. doi: 10.3390/ph16091197.
Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and the formation of atherosclerotic plaques is established by solid evidence. PCSK9 inhibitors have proven to be a valuable and practical resource for lowering the LDL cholesterol of many patients in recent years. Their inhibitory effect on atherosclerosis progression seems to be driven not just by lipid metabolism modification but also by LDL-independent mechanisms. We review the effect of PCSK9 inhibitors on various mechanisms involving platelet activation, inflammation, endothelial dysfunction, and the resultant clot formation. The main effectors of PCSK9 activation of platelets are CD36 receptors, lipoprotein(a), oxidised LDL particles, tissue factor, and factor VIII. Many more molecules are under investigation, and this area of research is growing rapidly.
动脉粥样硬化是心血管疾病的主要病理过程。低密度脂蛋白胆固醇(LDL胆固醇)与动脉粥样硬化斑块形成之间的联系已有确凿证据。近年来,前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂已被证明是降低许多患者LDL胆固醇的宝贵且实用的手段。它们对动脉粥样硬化进展的抑制作用似乎不仅由脂质代谢改变驱动,还由不依赖LDL的机制驱动。我们综述了PCSK9抑制剂对涉及血小板活化、炎症、内皮功能障碍及由此导致的血栓形成等各种机制的影响。PCSK9激活血小板的主要效应分子是CD36受体、脂蛋白(a)、氧化型LDL颗粒、组织因子和凝血因子VIII。还有更多分子正在研究中,这一研究领域正在迅速发展。