Apo E structure determines VLDL clearance and atherosclerosis risk in mice.

Published

Journal Article

We have generated mice expressing the human apo E4 isoform in place of the endogenous murine apo E protein and have compared them with mice expressing the human apo E3 isoform. Plasma lipid and apolipoprotein levels in the mice expressing only the apo E4 isoform (4/4) did not differ significantly from those in mice with the apo E3 isoform (3/3) on chow and were equally elevated in response to increased lipid and cholesterol in their diet. However, on all diets tested, the 4/4 mice had approximately twice the amount of cholesterol, apo E, and apo B-48 in their VLDL as did 3/3 mice. The 4/4 VLDL competed with human LDL for binding to the human LDL receptor slightly better than 3/3 VLDL, but the VLDL clearance rate in 4/4 mice was half that in 3/3 mice. On an atherogenic diet, there was a trend toward greater atherosclerotic plaque size in 4/4 mice compared with 3/3 mice. These data, together with our earlier observations in wild-type and human APOE*2-replacement mice, demonstrate a direct and highly significant correlation between VLDL clearance rate and mean atherosclerotic plaque size. Therefore, differences solely in apo E protein structure are sufficient to cause alterations in VLDL residence time and atherosclerosis risk in mice.

Full Text

Duke Authors

Cited Authors

  • Knouff, C; Hinsdale, ME; Mezdour, H; Altenburg, MK; Watanabe, M; Quarfordt, SH; Sullivan, PM; Maeda, N

Published Date

  • June 1999

Published In

Volume / Issue

  • 103 / 11

Start / End Page

  • 1579 - 1586

PubMed ID

  • 10359567

Pubmed Central ID

  • 10359567

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI6172

Language

  • eng

Conference Location

  • United States