Daintain/AIF-1 plays roles in coronary heart disease via affecting the blood composition and promoting macrophage uptake and foam cell formation

Cell Physiol Biochem. 2013;32(1):121-6. doi: 10.1159/000350130. Epub 2013 Jul 12.

Abstract

Background: Daintain/AIF-1 is an inflammatory polypeptide factor/allograft inflammatory factor 1 derived from macrophages. It is characterized in APOE(-/-) mice as a novel inflammatory factor associated with atherosclerosis. The purpose of this study was to characterize its function in human atherosclerosis.

Methods: Immunohistochemistry was used to identify the expression of daintain/AIF-1 in vessel segments within and far from atherosclerotic plaques; High-performance liquid chromatography (HPLC) was used to display the effects of daintain/AIF-1 on C-reactive protein (CRP), oxidative capacity and superoxide dismutase (SOD) in vivo; Oil Red O Staining was used to show the effects of daintain/AIF-1 on uptake of oxidized low density lipoprotein (ox-LDL) into U937 cells, a macrophage line; Western Blot was used to test scavenger receptor A (SRA) expression.

Results: A high density of daintain/AIF-1 was observed in the tunica intima and media of coronary artery with atherosclerotic plaque, and fewer daintain/AIF-1 in the vessels without atherosclerotic plaque; Daintain/AIF-1 injected intravenously into BALB/c mice boosted oxidative capacity, significantly impaired SOD activities and augmented the CRP level in blood. According to the oil red O test, daintain/AIF-1 profoundly facilitated the uptake of ox-LDL in U937 macrophages and formation of foam cells in the endothelium. We also found that the molecular mechanisms are effective by promoting overexpression of SRA on macrophages.

Conclusion: These findings implicate that the inflammatory factor daintain/AIF-1 is closely associated with atherogenesis, and could be further characterized as a novel risk factor for atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein
  • Calcium-Binding Proteins
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • DNA-Binding Proteins / metabolism*
  • Foam Cells / cytology*
  • Humans
  • Lipoproteins, LDL / metabolism
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microfilament Proteins
  • Scavenger Receptors, Class A / metabolism
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism
  • U937 Cells

Substances

  • AIF1 protein, human
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Lipoproteins, LDL
  • Microfilament Proteins
  • Scavenger Receptors, Class A
  • oxidized low density lipoprotein
  • C-Reactive Protein
  • Superoxide Dismutase