J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700336-JLR200 on January 14, 2008

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Journal of Lipid Research, Vol. 49, 773-781, April 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice

Lorraine Shelly, Lori Royer, Thomas Sand, Heather Jensen and Yi Luo1

Department of Cardiovascular, Metabolic, & Endocrine Diseases, Pfizer Global Research Division, Pfizer, Inc., Groton, CT 06340

Published, JLR Papers in Press, January 14, 2008.

1 To whom correspondence should be addressed. e-mail: yi.luo{at}pfizer.com

Phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids from triglyceride-rich lipoproteins into HDL. PLTP has been shown to be an important factor in lipoprotein metabolism and atherogenesis. Here, we report that chronic high-fat, high-cholesterol diet feeding markedly increased plasma cholesterol levels in C57BL/6 mice. PLTP deficiency attenuated diet-induced hypercholesterolemia by dramatically reducing apolipoprotein E-rich lipoproteins (–88%) and, to a lesser extent, LDL (–40%) and HDL (–35%). Increased biliary cholesterol secretion, indicated by increased hepatic ABCG5/ABCG8 gene expression, and decreased intestinal cholesterol absorption may contribute to the lower plasma cholesterol in PLTP-deficient mice. The expression of proinflammatory genes (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) is reduced in aorta of PLTP knockout mice compared with wild-type mice fed either a chow or a high-cholesterol diet. Furthermore, plasma interleukin-6 levels are significantly lower in PLTP-deficient mice, indicating reduced systemic inflammation. These data suggest that PLTP appears to play a proatherogenic role in diet-induced hyperlipidemic mice.

Supplementary key words ATP binding cassette transporter G5 • ATP binding cassette transporter G8 • cholesterol absorption

Abbreviations: apoA-I, apolipoprotein A-I; FPLC, fast-protein liquid chromatography; HFHC, high-fat, high-cholesterol; ICAM-1, intercellular adhesion molecule-1; IL-6, interleukin-6; PLTP, phospholipid transfer protein; SR-BI, scavenger receptor class B type I; VCAM-1, vascular cell adhesion molecule-1


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