Document Detail

Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease.
MedLine Citation:
PMID:  16458126     Owner:  NLM     Status:  MEDLINE    
Epidemiologic studies have shown that the concentration of high-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk. This identifies HDL-C as a potential therapeutic target. Compared with low-density lipoprotein cholesterol (LDL-C)-lowering agents, however, currently available HDL-raising drugs are relatively ineffective. Consequently, recent years have seen considerable efforts expended on identifying new drugs that can raise HDL-C. Cholesteryl ester transfer protein (CETP) plays an important role in cholesterol metabolism, being responsible for the transfer of cholesteryl esters from HDL to very low-density lipoproteins and LDLs. The observation that Japanese populations with CETP deficiency exhibited high levels of HDL-C has led to the concept that drugs targeting CETP activity may elevate HDL-C levels and potentially decrease cardiovascular risk. Support of this proposition has been obtained in rabbits where inhibition of CETP activity is markedly antiatherogenic. Two CETP inhibitors-torcetrapib and JTT-705-are currently in the preliminary stages of clinical development. Initial studies with these drugs in humans show that they substantially increase HDL-C levels and modestly decrease LDL-C levels. Larger, long-term, randomized, clinical end point trials are required to determine whether the beneficial effects of CETP inhibitors on lipoprotein metabolism can translate into reductions in cardiovascular events.
Philip J Barter; John J P Kastelein
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Publication Detail:
Type:  Journal Article; Review     Date:  2006-01-18
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  47     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-06     Completed Date:  2006-03-27     Revised Date:  2009-10-08    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  492-9     Citation Subset:  AIM; IM    
The Heart Research Institute, Camperdown, Sydney, Australia.
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MeSH Terms
Atherosclerosis / drug therapy*,  metabolism,  prevention & control
Cardiovascular Diseases / drug therapy*,  metabolism,  prevention & control
Carrier Proteins / antagonists & inhibitors*,  immunology,  metabolism
Cholesterol Ester Transfer Proteins
Cholesterol Esters
Cholesterol, HDL / metabolism
Cholesterol, LDL / metabolism
Glycoproteins / antagonists & inhibitors*,  immunology,  metabolism
Quinolines / therapeutic use
Risk Factors
Sulfhydryl Compounds / therapeutic use
Reg. No./Substance:
0/CETP protein, human; 0/Carrier Proteins; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol Esters; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Glycoproteins; 0/Quinolines; 0/Sulfhydryl Compounds; 0/Vaccines; 0/dalcetrapib; 262352-17-0/torcetrapib

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