PCSK9 INHIBITORS AS LDL CHOLESTEROL-LOWERING AGENTS: RATIONALE, CONCERNS AND PRELIMINARY OUTCOMES

被引：1

作者：

Costet, P. ^{[1
,2
]}

机构：

[1] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA

[2] CNRS UMR 6291, INSERM, UMR 1087, Nantes, France

来源：

DRUGS OF THE FUTURE | 2012年 / 37卷 / 05期

关键词：

LDL cholesterol; PCSK9; inhibitors; Cardiovascular disease; Hypercholesterolemia; SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN CHOLESTEROL; PLASMA PROPROTEIN CONVERTASE; FAMILIAL HYPERCHOLESTEROLEMIA; RECEPTOR DEGRADATION; RNA-INTERFERENCE; MUTATIONS; MICE; RISK; ASSOCIATION;

D O I：

10.1358/dof.2012.037.05.1790302

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Lowering cholesterol associated with low-density lipoprotein (LDL) is an efficient strategy to prevent cardiovascular diseases or attenuate their progression and damage. Statins have been successfully used for this purpose, but many patients still need alternative or additional, more aggressive therapy. Pro protein convertose subtilisin/kexin type 9 (PCSK9) inhibition may be the solution. The hypercholesterolemic effect of PCSK9 is due to its interaction with the LDL receptor (LDLR). Its absence leads to lower LDL cholesterol and reduced cardiovascular risk. However, the interaction of PCSK9 with other lipoprotein receptors and its presence in organs such as the brain raise concerns about its inhibitory effects. Several strategies have been developed to inhibit PCSK9 synthesis or its binding to the LDLR, and it is now being evaluated in clinical trials. Preliminary results are promising.

引用

页码：331 / 341

页数：11

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