SPONTANEOUS HYPERCHOLESTEROLEMIA AND ARTERIAL LESIONS IN MICE LACKING APOLIPOPROTEIN-E
SPONTANEOUS HYPERCHOLESTEROLEMIA AND ARTERIAL LESIONS IN MICE LACKING APOLIPOPROTEIN-E
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DOI：
10.1126/science.1411543
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发表时间：
1992-10-16
期刊：
影响因子：
56.9
通讯作者：
MAEDA, N
中科院分区：
文献类型：
--
作者：
ZHANG, SH;REDDICK, RL;MAEDA, N
载脂蛋白E（apoE）是清除乳糜微粒和极低密度脂蛋白残余物的受体的配体。因此，缺乏载脂蛋白E预计会导致血浆中富含胆固醇的残余物的积累，其延长的循环应该是致动脉粥样硬化的。通过基因靶向产生的ApoE缺陷小鼠被用来测试这一假设，并制作自发性动脉粥样硬化的小鼠模型。突变小鼠的血浆胆固醇是正常小鼠的5倍，并且在3个月大时在它们的近端腹侧动脉中形成了富含泡沫细胞的沉积物。这些自发性病变进展并在8个月时导致冠状动脉口严重闭塞。突变体的严重但可行的表型应该使他们有价值的研究遗传和环境因素，修改动脉粥样硬化的过程。
Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins. Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic. ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis. The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months. These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months. The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.