Increasing High-Density Lipoprotein Cholesterol Through Cholesteryl Ester Transfer Protein Inhibition: A Next Step in the Fight Against Cardiovascular Disease?

Author(s): W. A. Van der Steeg, K. El-Harchaoui, J. A. Kuivenhoven, J. J.P. Kastelein

Journal Name: Current Drug Targets - Cardiovascular & Hematological Disorders
Continued as Cardiovascular & Hematological Disorders-Drug Targets

Volume 5 , Issue 6 , 2005


Over the past decades, lowering of LDL-cholesterol (LDL-c) levels has been established as the foundation for preventing atherosclerotic disease. It is, however, widely accepted that additional risk reduction has to come from modifying other risk factors than LDL-c. In this context, increasing HDL-cholesterol (HDL-c) levels by pharmacological inhibition of the cholesteryl ester transfer protein (CETP) is currently under intense investigation. Two small-molecule compounds, JTT-705 and Torcetrapib, have been shown to effectively increase HDL-c levels in humans, without inducing clinically significant side effects when used as monotherapy or combined with statins. Whether this approach will translate into a reduction in risk of atherosclerotic disease has not yet been established. Data from studies focusing on genetic CETP deficiency as well as those studying the relationship between CETP plasma levels and risk of atherosclerosis do not provide clear answers. Several long-term clinical studies addressing this crucial issue have recently been initiated, results of which will follow within the next few years. This review focuses on CETP, its role in human lipid metabolism and its relation to atherosclerotic disease. Furthermore, it summarizes the currently available data regarding pharmacological CETP inhibition. Finally, it will highlight a number of issues basic to the considerations of whether CETP inhibition will fulfill its promises.

Keywords: Cholesteryl ester transfer protein (CETP), high-density lipoprotein cholesterol (HDL-c), atherosclerosis, JTT-705, torcetrapib

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Article Details

Year: 2005
Page: [481 - 488]
Pages: 8
DOI: 10.2174/156800605774961997
Price: $58

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