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Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease Barter PJ; Kastelein JJJ Am Coll Cardiol 2006[Feb]; 47 (3): 492-9Epidemiologic 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.|Amides[MESH]|Animals[MESH]|Atherosclerosis/*drug therapy/metabolism/prevention & control[MESH]|Cardiovascular Diseases/*drug therapy/metabolism/prevention & control[MESH]|Carrier Proteins/*antagonists & inhibitors/immunology/metabolism[MESH]|Cholesterol Ester Transfer Proteins[MESH]|Cholesterol Esters[MESH]|Cholesterol, HDL/metabolism[MESH]|Cholesterol, LDL/metabolism[MESH]|Esters[MESH]|Glycoproteins/*antagonists & inhibitors/immunology/metabolism[MESH]|Humans[MESH]|Quinolines/therapeutic use[MESH]|Risk Factors[MESH]|Sulfhydryl Compounds/therapeutic use[MESH]|Vaccines[MESH] |
