Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors contribute to distinct pharmacologic and pleiotropic actions

被引:132
作者
Mason, RP
Walter, MF
Day, CA
Jacob, RF
机构
[1] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA
[2] Elucida Res, Boston, MA USA
关键词
D O I
10.1016/j.amjcard.2005.06.008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Statin drugs inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and share the common mechanism of lowering circulating levels of low-density lipoprotein (LDL) cholesterol, a powerful indicator of risk for cardiovascular disease. Large clinical trials have documented the benefit of hypolipidemic therapy for both primary and secondary prevention of coronary artery disease and stroke. Recent clinical findings, including direct comparator studies, now indicate that certain statins may slow progression of disease at a rate and to an extent that cannot be solely attributed to LDL reduction. The proposed mechanisms for such pleiotropic actions include enhancement of endothelial-dependent nitric oxide bioavailability, anti-inflammatory activity, and inhibition of oxidative stress. To understand the biochemical basis for such differences among statins, this article reviews their physicochemical properties and pharmacology at the molecular level. 0 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:11F / 23F
页数:13
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