PCSK9 and Lipid Metabolism: Genetic Variants, Current Therapies, and Cardiovascular Outcomes.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2024-06-22 DOI:10.1007/s10557-024-07599-5

Daniela Grejtakova, Iveta Boronova, Jarmila Bernasovska, Stefano Bellosta

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引用次数: 0

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in the modulation of lipid metabolism as a critical negative regulator of hepatic low-density lipoprotein receptor (LDLR) levels and circulating low-density lipoprotein (LDL) clearance. Numerous gain-of-function (GOF) mutations in PCSK9 have been identified as causing familial hypercholesterolemia (FH) by reducing LDLR levels, and loss-of-function (LOF) mutations associated with a hypercholesterolemia phenotype protective against atherosclerosis. PCSK9 represents an example of successful translational research resulting in the identification of PCSK9 as a major drug target for a lipid-lowering therapy. To explore the genetic constitution of PCSK9 and its biologic role, in this review, we summarize the current evidence of clinically significant PCSK9 genetic variants involved in lipid metabolism as well as emphasize the importance of PCSK9 inhibition for the improvement of cardiovascular outcomes by conducting a meta-analysis of the available data on the incidence of cardiovascular disease events.

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PCSK9 与脂质代谢：遗传变异、当前疗法和心血管预后。

Proprotein convertase subtilisin/kexin type 9 (PCSK9)作为肝脏低密度脂蛋白受体（LDLR）水平和循环低密度脂蛋白（LDL）清除率的关键负调控因子，在调节脂质代谢方面发挥着至关重要的作用。PCSK9 中的许多功能增益（GOF）突变已被确定为可通过降低 LDLR 水平导致家族性高胆固醇血症（FH），而功能缺失（LOF）突变则与可防止动脉粥样硬化的高胆固醇血症表型有关。PCSK9 是转化研究的一个成功范例，它使 PCSK9 成为降脂疗法的主要药物靶点。为了探究 PCSK9 的基因构成及其生物作用，我们在本综述中总结了参与脂质代谢的具有临床意义的 PCSK9 基因变异的现有证据，并通过对心血管疾病事件发生率的现有数据进行荟萃分析，强调了抑制 PCSK9 对改善心血管预后的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.