INCREASED ATHEROSCLEROSIS IN MICE RECONSTITUTED WITH APOLIPOPROTEIN-ENULL MACROPHAGES

Macrophage-derived foam cells express apolipoprotein E (apoE) abundant ly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplanta tion 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 ather ogenic diet, C57BL/6 mice reconstituted with apoE null marrow develope d 10-fold more atherosclerosis than controls in the absence of signifi cant differences in serum cholesterol levels or lipoprotein profiles, ApoE expression was absent in the macrophage-derived foam cells of C57 BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expr ession by the macrophage promotes foam cell formation, These data supp ort a protective role for apoE expression by the macrophage in early a therogenesis.