Ugovšek Sabina, Šebeštjen Miran
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Department of Cardiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
J Clin Med. 2022 Jun 23;11(13):3625. doi: 10.3390/jcm11133625.
Elevated low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)) levels have an important role in the development and progression of atherosclerosis, followed by cardiovascular events. Besides statins and other lipid-modifying drugs, PCSK9 monoclonal antibodies are known to reduce hyperlipidemia. PCSK9 monoclonal antibodies decrease LDL cholesterol levels through inducing the upregulation of the LDL receptors and moderately decrease Lp(a) levels. In addition, PCSK9 monoclonal antibodies have shown non-lipid effects. PCSK9 monoclonal antibodies reduce platelet aggregation and activation, and increase platelet responsiveness to acetylsalicylic acid. Evolocumab as well as alirocumab decrease an incidence of venous thromboembolism, which is associated with the decrease of Lp(a) values. Besides interweaving in haemostasis, PCSK9 monoclonal antibodies play an important role in reducing the inflammation and improving the endothelial function. The aim of this review is to present the mechanisms of PCSK9 monoclonal antibodies on the aforementioned risk factors.
低密度脂蛋白(LDL)胆固醇和脂蛋白(a)[Lp(a)]水平升高在动脉粥样硬化的发生和发展中起重要作用,随后会引发心血管事件。除了他汀类药物和其他调脂药物外,已知前蛋白转化酶枯草溶菌素9(PCSK9)单克隆抗体可降低高脂血症。PCSK9单克隆抗体通过诱导LDL受体上调来降低LDL胆固醇水平,并适度降低Lp(a)水平。此外,PCSK9单克隆抗体已显示出非脂质效应。PCSK9单克隆抗体可减少血小板聚集和活化,并增加血小板对乙酰水杨酸的反应性。依洛尤单抗和阿利西尤单抗均可降低静脉血栓栓塞的发生率,这与Lp(a)值的降低有关。除了参与止血外,PCSK9单克隆抗体在减轻炎症和改善内皮功能方面也发挥着重要作用。本综述的目的是阐述PCSK9单克隆抗体对上述危险因素的作用机制。