Dietary cholesterol plays a role in cd36-mediated atherogenesis in LDLR-knockout mice

David J. Kennedy, Sai D. Kuchibhotla, Ella Guy, Young Mi Park, George Nimako, Difernando Vanegas, Richard E. Morton, Maria Febbraio

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

OBJECTIVE-: CD36 has been shown to play a role in atherosclerosis in the apolipoprotein E-knockout (apoE) mouse. We observed no difference in aortic lesion area between Western diet (WD)-fed LDLR and LDLR/CD36 mice. The objective was to understand the mechanism of CD36-dependent atherogenesis. METHODS AND RESULTS-: ApoE mice transplanted with bone marrow from LDLR/CD36 mice had significantly less aortic lesion compared with those transplanted with LDLR marrow. Reciprocal macrophage transfer into hyperlipidemic apoE and LDLR animals showed that foam cell formation induced by in vivo modified lipoproteins was dependent on the lipoprotein, not macrophage type. LDLR and LDLR/CD36 mice were fed a cholesterol-enriched diet (HC), and we observed significant lesion inhibition in LDLR/CD36 mice. LDL/plasma isolated from HC-fed LDLR mice induced significantly greater jnk phosphorylation, cytokine release, and reactive oxygen species secretion than LDL/plasma from WD-fed LDLR mice, and this was CD36-dependent. HC-fed LDLR mice had higher circulating levels of cytokines than WD-fed mice. CONCLUSIONS-: These data support the hypothesis that CD36-dependent atherogenesis is contingent on a proinflammatory milieu that promotes the creation of specific CD36 ligands, not solely hypercholesterolemia, and may explain the greater degree/accelerated rate of atherosclerosis observed in syndromes associated with inflammatory risk.

Original languageEnglish
Pages (from-to)1481-1487
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number10
DOIs
StatePublished - Oct 2009

Keywords

  • Atherosclerosis
  • CD36
  • Inflammation
  • Murine models
  • Scavenger receptor

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