Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage lipid accumulation in a CD36 and scavenger receptor class A-dependent manner

Zhenze Zhao, Maria C. De Beer, Lei Cai, Reto Asmis, Frederick C. De Beer, Willem J.S. De Villiers, Deneys R. Van Der Westhuyzen

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Objective - To investigate the potential of circulating low-density lipoprotein (LDL), isolated from apolipoprotein E (apoE)-deficient mice (E-/-LDL) and from LDL receptor-deficient mice (Lr-/-LDL), to induce foam cell formation. Methods and Results - Binding studies using COS-7 cells overexpressing CD36, J774 cells, and mouse peritoneal macrophages (MPMs) unexpectedly showed for the first time that E-/-LDL, which is enriched in cholesterol, is a high-affinity ligand for CD36 and exhibited greater macrophage uptake than Lr-/-LDL or normal LDL. Minimal copper-mediated oxidization of Lr-/-LDL or C57LDL in vitro resulted in increased ligand internalization, although cell uptake of these oxidized LDLs was lower than that of E-/-LDL, even at oxidation levels similar to that found in E-/-LDL. Treatment of MPMs with E-/-LDL and Lr-/-LDL (to a 2- to 3-fold lesser extent), but not normal LDL, resulted in significant cellular cholesteryl ester accumulation and foam cell formation. Experiments using MPMs lacking CD36, scavenger receptor class A (SR-A), or both, indicated a major contribution of CD36 (≈50%), and to a lesser extent, SR-A (24% to 30%), to E-/-LDL uptake. Conclusions - Because of its increased state of oxidation and high cholesterol content, LDL in apoE-deficient mice acts in a proatherogenic manner, without requiring further modification in the vascular wall, to induce foam cell formation through its uptake by scavenger receptors.

Original languageEnglish (US)
Pages (from-to)168-173
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2005

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Keywords

  • Apolipoprotein E
  • CD36
  • Macrophages
  • SR-A
  • Scavenger receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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