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Journal of Lipid Research, Vol. 47, 2400-2407, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice

Wen-Jun Wang^*, Juan M. Baez, Rie Maurer^*, Hayes M. Dansky^1, and David E. Cohen^2,*,**

^* Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
Department of Medicine, Columbia University, New York, NY 10032
^** Division of Health and Sciences and Technology, Harvard-Massachusetts Institute of Technology, Boston, MA 02115

Published, JLR Papers in Press, August 28, 2006.

¹ Present address of H. M. Dansky: Experimental Medicine, Merck & Co., Inc., RY34-A400, P.O. Box 2000, Rahway, NJ 07065.

² To whom correspondence should be addressed. e-mail: dcohen{at}partners.org

Phosphatidylcholine transfer protein (PC-TP) is a cytosolic phospholipid binding protein and a member of the steroidogenic acute regulatory-related transfer domain superfamily. Its tissue distribution includes liver and macrophages. PC-TP regulates hepatic lipid metabolism, and its absence in cholesterol-loaded macrophages is associated with reduced ATP binding cassette transporter A1-mediated lipid efflux and increased susceptibility to apoptosis induced by unesterified cholesterol. To explore a role for PC-TP in atherosclerosis, we prepared PC-TP-deficient/apolipoprotein E-deficient (Pctp^–/–/Apoe^–/–) mice and littermate Apoe^–/– controls. At 16 weeks, atherosclerosis was increased in chow-fed male, but not female, Pctp^–/–/Apoe^–/– mice. This effect was associated with increases in plasma lipid concentrations. By contrast, no differences in atherosclerosis were observed between male or female Pctp^–/–/Apoe^–/– mice and Apoe^–/– controls fed a Western-type diet for 16 weeks. At 24 weeks, atherosclerosis in chow-fed male Pctp^–/–/Apoe^–/– mice tended to be reduced in proportion to plasma cholesterol. The attenuation of atherosclerosis in female Pctp^–/–/Apoe^–/– mice fed chow or the Western-type diet for 24 weeks was not attributable to changes in plasma cholesterol or triglyceride concentrations. These findings suggest that PC-TP modulates the development of atherosclerosis, in part by regulating plasma lipid concentrations.

Supplementary key words phosphatidylcholine transfer protein • steroidogenic acute regulatory-related transfer domain • cholesterol • triglycerides • aorta • macrophage

Abbreviations: apoE, apolipoprotein E; PC-TP, phosphatidylcholine transfer protein; START, steroidogenic acute regulatory-related transfer

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