Novel HDL-directed pharmacotherapeutic strategies

被引:123
作者
Degoma, Emil M. [1 ]
Rader, Daniel J. [2 ]
机构
[1] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Med, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA
关键词
ESTER TRANSFER PROTEIN; HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; LIVER-X-RECEPTOR; REVERSE CHOLESTEROL TRANSPORT; CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; DIET-INDUCED ATHEROSCLEROSIS; B-CONTAINING LIPOPROTEINS; ENDOTHELIAL LIPASE GENE;
D O I
10.1038/nrcardio.2010.200
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The burden of atherothrombotic cardiovascular disease remains high despite currently available optimum medical therapy. To address this substantial residual risk, the development of novel therapies that attempt to harness the atheroprotective functions of HDL is a major goal. These functions include the critical role of HDL in reverse cholesterol transport, and its anti-inflammatory, antithrombotic, and antioxidant activities. Discoveries in the past decade have shed light on the complex metabolic and antiatherosclerotic pathways of HDL. These insights have fueled the development of HDL-targeted drugs, which can be classified among four different therapeutic approaches: directly augmenting apolipoprotein A-I (apo A-I) levels, such as with apo A-I infusions and upregulators of endogenous apo A-I production; indirectly augmenting apo A-I and HDL-cholesterol levels, such as through inhibition of cholesteryl ester transfer protein or endothelial lipase, or through activation of the high-affinity niacin receptor GPR109A; mimicking the functionality of apo A-I with apo A-I mimetic peptides; and enhancing steps in the reverse cholesterol transport pathway, such as via activation of the liver X receptor or of lecithin-cholesterol acyltransferase.
引用
收藏
页码:266 / 277
页数:12
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