Reddick R L, Zhang S H, Maeda N
Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525.
Arterioscler Thromb. 1994 Jan;14(1):141-7. doi: 10.1161/01.atv.14.1.141.
Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.
载脂蛋白E缺陷小鼠的血浆总胆固醇和甘油三酯会自发升高，高密度脂蛋白降低。这些小鼠会以时间依赖性方式形成动脉病变。病变分布在幼鼠的主动脉窦中最为集中，而在8至9个月大的小鼠中，病变广泛分布于整个动脉树。在幼鼠中，主动脉窦内靠近瓣膜附着部位存在内皮下泡沫细胞沉积。到5个月大时，泡沫细胞沉积、游离胆固醇和混合的平滑肌细胞构成了正在形成的动脉粥样硬化病变。8至9个月大后，动脉病变显示出复杂性增加，出现了纤维帽病变。透射电子显微镜显示斑块内有泡沫细胞、平滑肌细胞（收缩型和合成型）、细胞碎片和针状胆固醇沉积。通过扫描电子显微镜观察，主动脉窦和升主动脉内存在内皮下泡沫细胞聚集。结果表明，这些载脂蛋白E缺陷小鼠中形成的动脉粥样硬化病变的复杂性与其他物种中描述的相似，因此是研究遗传和环境对动脉粥样硬化过程影响的重要模型。
