Enhanced aortic macrophage lipid accumulation and inflammatory response in KDI receptor null mice fed an atherogenic diet

Shu Wang, Dayong Wu, Nirupa R. Matthan, Stefania Lamon-Fava, Jaime L. Lecker, Alice H. Lichtenstein

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The effect of an atherogenic diet on inflammatory response and elicited peritoneal macrophage (Mφ) cholesterol accumulation in relation to aortic lesion formation was assessed in LDL receptor null (LDLr-/-) mice. Mice were fed an atherogenic or control diet for 32 weeks. The atherogenic relative to control diet resulted in significantly higher plasma monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) concentrations, more aortic wall Mφ deposition, higher serum non HDL-cholesterol concentrations and total cholesterol to HDL-cholesterol ratios, and greater accumulation of both aortic free and esterified cholesterol. Elicited peritoneal Mφ selectively accumulated longer chain unsaturated fatty acids in their membrane, independent of the dietary fatty acid profile. Elicited peritoneal Mφ isolated from mice fed the atherogenic relative to control diet had significantly less arachi-donic acid levels, accumulated significantly higher esterified cholesterol, had significantly higher mRNA levels and secretion of MCP-1, and mRNA and protein levels of ATP-binding cassette A1. Diet treatment had no significant effect in elicited peritoneal Mφ on TNFα and IL-6 mRNA levels and secretion. These data suggest that the atherogenic relative to control diet resulted in higher plasma inflammatory factor concentrations, less favorable lipoprotein profile, higher elicited peritoneal Mφ cholesterol accumulation and inflammatory factor secretion, and more aortic wall Mφ deposition, which in turn were associated with greater aortic cholesterol accumulation.

Original languageEnglish
Pages (from-to)701-711
Number of pages11
JournalLipids
Volume45
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • Atherogenic diet
  • Atherosclerosis
  • Cholesterol accumulation
  • Inflammatory response Macrophage
  • LDLr-/-mouse

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