Human LDL receptor enhances sequestration of ApoE4 and VLDL remnants on the surface of hepatocytes but not their internalization in mice.

ABSTRACT:

Objective

In humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR).

Methods and results

Primary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-dens

SUBMITTER: Altenburg M 

PROVIDER: S-EPMC5268126 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature