Dietary Cholesterol Plays a Role in CD36-Mediated Atherogenesis in LDLR-Knockout Mice Article (Web of Science)


  • Objective— CD36 has been shown to play a role in atherosclerosis in the apolipoprotein E-knockout ( apoE o ) mouse. We observed no difference in aortic lesion area between Western diet (WD)-fed LDLR o and LDLR o / CD36 o mice. The objective was to understand the mechanism of CD36-dependent atherogenesis. Methods and Results— A poE o mice transplanted with bone marrow from LDLR o / CD36 o mice had significantly less aortic lesion compared with those transplanted with LDLR o marrow. Reciprocal macrophage transfer into hyperlipidemic apoE o and LDLR o animals showed that foam cell formation induced by in vivo modified lipoproteins was dependent on the lipoprotein, not macrophage type. LDLR o and LDLR o / CD36 o mice were fed a cholesterol-enriched diet (HC), and we observed significant lesion inhibition in LDLR o / CD36 o mice. LDL/plasma isolated from HC-fed LDLR o mice induced significantly greater jnk phosphorylation, cytokine release, and reactive oxygen species secretion than LDL/plasma from WD-fed LDLR o mice, and this was CD36-dependent. HC-fed LDLR o 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.


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

publication date

  • 2009

number of pages

  • 6

start page

  • 1481

end page

  • 1487


  • 29


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