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

نویسندگان

  • Zhenze Zhao
  • Maria C de Beer
  • Lei Cai
  • Reto Asmis
  • Frederick C de Beer
  • Willem J S de Villiers
  • Deneys R van der Westhuyzen
چکیده

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 ( approximately 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.

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عنوان ژورنال:
  • Arteriosclerosis, thrombosis, and vascular biology

دوره 25 1  شماره 

صفحات  -

تاریخ انتشار 2005