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Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.


Fazio SS , Babaev VR V R , Murray AB A B , Hasty AH A H , Carter KJ K J , Gleaves LA L A , Atkinson JB J B , Linton MF M F . Proceedings of the National Academy of Sciences of the United States of America. 1997 4 29; 94(9). 4647-52


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.