Pleiotropic Effects of PCSK-9 Inhibitors.
Pleiotropic Effects of PCSK-9 Inhibitors.
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DOI：
10.3390/ijms22063144
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发表时间：
2021-03-19
影响因子：
5.6
通讯作者：
Okopień B
中科院分区：
文献类型：
--
作者：
Basiak M;Kosowski M;Cyrnek M;Bułdak Ł;Maligłówka M;Machnik G;Okopień B
前蛋白转化酶枯草杆菌蛋白酶/kexin 9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，减少低密度脂蛋白受体（LDL-R）的降解，从而增加低密度脂蛋白胆固醇（LDLc）从血流中的摄取并降低其浓度。已经证实了三种单克隆抗体，即alirocumab（人IgG 1/κ单克隆抗体，在中国仓鼠卵巢细胞中进行基因工程改造）、evolocumab（第一种全人源单克隆抗体）和bococizumab（人源化小鼠抗体）在抑制PCSK-9作用和降低LDLc水平方面的有效性。前两种药物在临床试验后获得美国食品药品监督管理局（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病例。目前，它们被用作单药治疗，并与他汀类药物和依折麦布联合使用，以加强治疗并根据美国心脏协会（AHA）和欧洲心脏病学会（ESC）指南实现治疗目标。然而，降脂作用并不是研究人员描述的PCSK-9抑制剂的唯一作用。本文综述了描述PCSK-9抑制剂的多效性作用的文献，PCSK-9抑制剂属于一组正在越来越多地使用的药物，特别是当标准降脂治疗失败时。本文重点介绍了除降脂外的其他活性，如抗动脉粥样硬化作用和动脉粥样硬化斑块的稳定性、抗聚集作用、抗凝作用、抗血栓作用和影响细菌感染过程的能力。在本出版物中，我们试图系统地回顾当前的科学数据，这些数据来自我们自己的科学工作和国际出版物的知识。
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.
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