Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages

Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atheroscleratic 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.