J. Lipid Res.
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A more recent version of this article appeared on July 1, 2003

Papers In Press, published online ahead of print April 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300062-JLR200
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Submitted on February 5, 2003
Revised on March 20, 2003
Accepted on April 14, 2003

Phosphatidylinositol promotes cholesterol transport and excretion

Jim W. Burgess, Jonathan Boucher, Tracey A-M Neville, Patricia Rouillard, Christopher Stamler, Susha Zachariah, and Daniel L. Sparks

University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7

Corresponding Author: dsparks{at}ottawaheart.ca

Administration of phosphatidylinositol (PI) into NZW rabbits increases HDL negative charge and stimulates reverse cholesterol transport. Intravenously administered PI (10 mg/kg) associated almost exclusively with the HDL fraction in rabbits. PI promoted an increase in the hepatic uptake of plasma free cholesterol and a 21-fold increase in the biliary secretion of plasma derived cholesterol. PI also increased cholesterol excretion into the feces by 2.5-fold. PI directly affects cellular cholesterol metabolism. In cholesterol loaded macrophages, PI stimulated cholesterol mass efflux to lipid-poor reconstituted HDL. PI was about half as effective as cAMP at stimulating efflux and the effects of cAMP and PI were additive. In cultured HepG2 cells, PI-enriched HDL also enhanced free cholesterol uptake from HDL by 3-fold and decreased cellular cholesterol synthesis and esterification. PI-enrichment had no effect on the selective uptake of cholesterol esters or on the internalization of HDL particles. PI-dependent metabolic events were efficiently blocked by inhibitors of protein kinase C and the inositol signaling cascade. The data suggests that HDL-PI acts via cell surface ABC transporters and signaling pathways to regulate both cellular and intravascular cholesterol homeostasis.


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J. Lipid Res.Home page
J. W. Burgess, T. A-M. Neville, P. Rouillard, Z. Harder, D. S. Beanlands, and D. L. Sparks
Phosphatidylinositol increases HDL-C levels in humans
J. Lipid Res., February 1, 2005; 46(2): 350 - 355.
[Abstract] [Full Text] [PDF]




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