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Journal of Lipid Research, Vol. 50, S201-S206, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Lipoprotein Metabolism

The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis

David Masson^1,*,, Xian-Cheng Jiang, Laurent Lagrost and Alan R. Tall^*

^* Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032
INSERM, Centre de Recherche-Unite Mixte de Recherche 866, Faculté de Médecine, Institut Fédératif de Recherche Santé-Sciences et Technologies de l' Information et de la Communication, Université de Bourgogne, 21079 Dijon, France
Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 11203

D.M. is supported by a grant from the Philippe Foundation.

Published, JLR Papers in Press, November 20, 2008.

¹ To whom correspondence should be addressed. e-mail: dm2561{at}columbia.edu or david.masson{at}chu-dijon.fr

ABSTRACT

The plasma lipid transfer proteins promote the exchange of neutral lipids and phospholipids between the plasma lipoproteins. Cholesteryl ester transfer protein (CETP) facilitates the removal of cholesteryl esters from HDL and thus reduces HDL levels, while phospholipid transfer protein (PLTP) promotes the transfer of phospholipids from triglyceride-rich lipoproteins into HDL and increases HDL levels. Studies in transgenic mouse models and in humans with rare genetic deficiencies (CETP) or common genetic variants (CETP and PLTP) highlight the central role of these molecules in regulating HDL levels. Human CETP deficiency is associated with dramatic elevations of HDL cholesterol and apolipoprotein A-I levels, while PLTP variants with increased expression are associated with higher HDL levels. A recent meta-analysis suggests that common CETP alleles causing reduced CETP and increased HDL levels are associated with reduced coronary heart disease. The failure of a clinical trial with the CETP inhibitor torcetrapib may have been related in part to off-target toxicity. Ongoing phase 3 clinical trials with other CETP inhibitors may help to clarify if this strategy can ultimately be successful in the treatment of atherosclerosis.

Supplementary key words cholesteryl ester transfer protein • phospholipid transfer protein • high density lipoproteins • low density lipoproteins

Abbreviations: apo, apolipoprotein; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; CHD, coronary heart disease; LPS, lipopolysaccharide; PLTP, phospholipid transfer protein; TG, triglyceride

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