Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.

Fazio S, Babaev VR, Murray AB, Hasty AH, Carter KJ, Gleaves LA, Atkinson JB, Linton MF
Proc Natl Acad Sci U S A. 1997 94 (9): 4647-52

PMID: 9114045 · PMCID: PMC20778 · 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.

MeSH Terms (13)

Animals Aorta Apolipoproteins E Arteriosclerosis Bone Marrow Transplantation Cholesterol Diet, Atherogenic Female Lipoproteins Macrophages Mice Mice, Inbred C57BL Mice, Mutant Strains

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