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Abstract：
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.
摘要：
前蛋白转化酶枯草杆菌蛋白酶/kexin9型（PCSK-9）抑制剂是一组药物，其主要作用机制是与PCSK-9分子结合，这减少了低密度脂蛋白受体（LDL-R）的降解，因此，增加血液中低密度脂蛋白胆固醇（LDLc）的摄取，并降低其浓度。三种单克隆抗体的有效性，即,alirocumab（人IgG1/κ单克隆抗体，中国仓鼠卵巢细胞基因工程），evolocumab（第一个完全人类单克隆抗体），和bococizumab（人源化小鼠抗体），已证实抑制PCSK-9的作用和降低LDLc水平。前两个,经过临床试验,已获得食品和药物管理局（FDA）的批准，主要用于治疗常染色体家族性高胆固醇血症和他汀类药物不耐受的情况。目前，它们既用作单一疗法，也与他汀类药物和依泽替米贝联合使用，以按照美国心脏协会（AHA）和欧洲心脏病学会（ESC）指南加强治疗并实现治疗目标。然而,降脂作用并不是研究人员描述的PCSK-9抑制剂具有的唯一作用。本文综述了PCSK-9抑制剂的多效性文献,属于越来越多使用的一组药物，尤其是标准降脂治疗失败时。文章重点介绍降脂以外的其他活动，如抗动脉粥样硬化作用和动脉粥样硬化斑块的稳定，抗聚集效果，抗凝作用，抗肿瘤作用,以及影响细菌感染进程的能力。在本出版物中,我们试图系统地回顾当前的科学数据，来自我们自己的科学工作和国际出版物的知识。
