Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages
Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages
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DOI：
10.1073/pnas.94.9.4647
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Linton, MF
中科院分区：
文献类型：
--
作者：
Fazio, S;Babaev, VR;Linton, MF
巨噬细胞源性泡沫细胞在动脉粥样硬化病变中大量表达载脂蛋白E（apoE）。为了检测巨噬细胞分泌apoE在动脉粥样硬化形成中的生理作用，使用骨髓移植来用apoE基因无效或野生型的巨噬细胞重建C57 BL/6小鼠。在致动脉粥样硬化饮食13周后，用apoE缺失型骨髓重建的C57 BL/6小鼠发育为10- 20个月。在血清胆固醇水平或脂蛋白谱没有显著差异的情况下，在用apoE缺失骨髓重建的C57 BL/6小鼠的巨噬细胞源性泡沫细胞中不存在ApoE表达。因此，缺乏apoE表达的巨噬细胞促进泡沫细胞的形成，这些数据支持apoE表达的巨噬细胞在早期动脉粥样硬化的保护作用。
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.