The promises of PCSK9 inhibition

被引：19

作者：

Petrides, Francine ^{[1
]}

Shearston, Kate ^{[1
]}

Chatelais, Mathias ^{[2
]}

Guilbaud, Florian ^{[2
]}

Meilhac, Olivier ^{[3
]}

Lambert, Gilles ^{[1
,2
,4
]}

机构：

[1] Univ New S Wales, Sydney, NSW, Australia

[2] Lab Inserm UMR957, Nantes, France

[3] Hop Bichat Claude Bernard, Lab Inserm UMR698, F-75877 Paris, France

[4] Univ Nantes, Fac Med, Nantes, France

来源：

CURRENT OPINION IN LIPIDOLOGY | 2013年 / 24卷 / 04期

基金：

英国医学研究理事会;

关键词：

cardiovascular disease; clinical trial; LDL receptor; monoclonal antibodies; PCSK9; SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN-RECEPTOR; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; MONOCLONAL-ANTIBODY; CHOLESTEROL LEVELS; MOLECULAR CHARACTERIZATION; LDL CHOLESTEROL; SERINE-PROTEASE; PLASMA PCSK9; DOUBLE-BLIND;

D O I：

10.1097/MOL.0b013e328361f62d

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Purpose of review In the past 10 years, the LDL receptor inhibitor proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a validated target for lowering plasma LDL cholesterol levels. Here we review the most recent reports on PCSK9 out of a total of 500 publications published in print or online before March 2013 and indexed on PubMed. Recent findings All published in 2012, phase I and II clinical trials demonstrate that fully human monoclonal antibodies targeting PCSK9 dramatically reduce LDL-C and enable patients to reach their target goals, without severe or serious safety issues. Summary This review summarizes the discovery of PCSK9, its original mode of action as a secreted inhibitor of the LDL receptor, as well as its genetic regulation by statins. We then focus on the major results from the 2012 phase I and II PCSK9 inhibitor clinical trials. We also review the recent in-vivo studies demonstrating the potential cardiovascular benefits of long-term PCSK9 inhibition and discuss its potential side-effects.

引用

页码：307 / 312

页数：6

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