Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages

作者：Sergio Fazio, Vladimir R. Babaev, Alisa B. Murray, Alyssa H. Hasty, Kathy J. Carter, Linda A. Gleaves, James B. Atkinson, MacRae F. Linton · 发表于：Proceedings of the National Academy of Sciences · 年份：1997 · DOI：10.1073/pnas.94.9.4647 · 被引用次数：291 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Peroxisome Proliferator-Activated Receptors、Adipokines, Inflammation, and Metabolic Diseases

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.