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A more recent version of this article appeared on November 1, 2002

Papers In Press, published online ahead of print August 16, 2002
J. Lipid Res., doi:10.1194/jlr.M200172-JLR200
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Submitted on April 22, 2002
Revised on July 23, 2002
Accepted on July 31, 2002

Evidence for differential effects of apolipoproteins E3 and E4 on HDL metabolism

Paul C.R. Hopkins, Yadong Huang, James G. McGuire, and Robert E. Pitas

Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100

Corresponding Author: eokeeffe{at}gladstone.ucsf.edu

We present a murine model that examines the effects of macrophage-produced apoE3 and apoE4 on very low density lipoprotein (VLDL) and high density lipoprotein (HDL) metabolism. Mice expressing apoE3 on the Apoe–/– background had substantially lower VLDL levels than mice expressing apoE4. In addition, there were differences between the HDL of apoE3- and apoE4-expressing mice. Apoe–/– mice have low levels of HDL. Low level expression of either apoE3 or apoE4 were able to restore near-normal HDL levels, which increased dramatically when the mice were challenged with a high-fat diet. ApoE4-expressing mice had smaller HDL than apoE3-expressing mice on both chow and high fat diets. In addition, plasma from apoE4-expressing mice was less efficient at transferring apoAI from VLDL to HDL and at generating HDL in vitro than that from apoE3-expressing mice. Thus, we present experimental evidence for differential effects of apoE3 and apoE4 on HDL metabolism that support epidemiological observations made in humans, which suggested that individual homozygous for the epsilon 4 allele had lower HDL than others.


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