Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages

Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4647-52. doi: 10.1073/pnas.94.9.4647.


Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / pathology
  • Apolipoproteins E / biosynthesis
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Arteriosclerosis / etiology
  • Arteriosclerosis / genetics
  • Arteriosclerosis / metabolism*
  • Bone Marrow Transplantation
  • Cholesterol / blood
  • Diet, Atherogenic
  • Female
  • Lipoproteins / blood
  • Macrophages / metabolism*
  • Macrophages / transplantation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains


  • Apolipoproteins E
  • Lipoproteins
  • Cholesterol