Evidence for differential effects of apoE3 and apoE4 on HDL metabolism

We present a murine model that examines the ef- fects of macrophage-produced apolipoprotein E3 (apoE3) and apoE4 on VLDL and high density lipoprotein (HDL) metabolism. Mice expressing apoE3 on the Apoe � / � back- ground had substantially lower VLDL levels than mice ex- pressing apoE4. In addition, there were differences be- tween the HDL of apoE3- and apoE4-expressing mice. Apoe � / � mice have low levels of HDL. Low level expression of either apoE3 or apoE4 was 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-express- ing mice was less efficient at transferring apoA-I from VLDL to HDL and at generating HDL in vitro than that from apoE3-expressing mice. Thus, we present experi- mental evidence for differential effects of apoE3 and apoE4 on HDL metabolism that supports epidemiological observations made in humans, which suggested that individ- ual homozygous for the � 4 allele had lower HDL than oth- ers. —Hopkins, P. C. R., Y. Huang, J. G. McGuire, and R. E. Pitas. Evidence for differential effects of apoE3 and apoE4 on HDL metabolism. J. Lipid Res. 2002. 43: 1881-1889.