J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

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

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M700336-JLR200v1
49/4/773    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Shelly, L.
Right arrow Articles by Luo, Y.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shelly, L.
Right arrow Articles by Luo, Y.
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






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.