Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:160-167
Published online before print January 2, 2003, doi: 10.1161/01.ATV.0000054658.91146.64
Published online before print January 2, 2003, doi: 10.1161/01.ATV.0000054658.91146.64
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© 2003 American Heart Association, Inc.
Brief Review |
Cholesteryl Ester Transfer Protein
A Novel Target for Raising HDL and Inhibiting Atherosclerosis
From the Hanson Institute and the Department of Cardiology (P.J.B.), Royal Adelaide Hospital, Adelaide, Australia; the National Heart, Lung, and Blood Institute (H.B.B. Jr), National Institutes of Health, Bethesda, Md; the National Institute for Health and Medical Research and Hopital de la Pitie (M.J.C.), Paris, France; the Preventive Cardiology and Lipid Clinic (D.J.R.), University of Pennsylvania Medical Center, Philadelphia; the Mount Sinai Medical Center–Miami Heart Institute and the Departments of Medicine and Epidemiology and of Public Health (C.H.H.), University of Miami School of Medicine, Miami, Fla; and the Division of Molecular Medicine (A.R.T.), Department of Medicine, Columbia University, New York, NY.
Correspondence to Prof Philip J. Barter, The Heart Research Institute, 145 Missenden Rd, Camperdown, Sydney, Australia 2050. E-mail p.barter{at}hri.org.au
Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from antiatherogenic HDLs to proatherogenic apolipoprotein B (apoB)–containing lipoproteins, including VLDLs, VLDL remnants, IDLs, and LDLs. A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. Studies in rabbits, a species with naturally high levels of CETP, support the therapeutic potential of CETP inhibition as an approach to retarding atherogenesis. Studies in mice, a species that lacks CETP activity, have provided mixed results. Human subjects with heterozygous CETP deficiency and an HDL cholesterol level >60 mg/dL have a reduced risk of coronary heart disease. Evidence that atherosclerosis may be increased in CETP-deficient subjects whose HDL levels are not increased is difficult to interpret and may reflect confounding or bias. Small-molecule inhibitors of CETP have now been tested in human subjects and shown to increase the concentration of HDL cholesterol while decreasing that of LDL cholesterol and apoB. Thus, it seems important and timely to test the hypothesis in randomized trials of humans that pharmacological inhibition of CETP retards the development of atherosclerosis.
Key Words: HDL • LDL • reverse cholesterol transport • genetic CETP deficiency
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