APOE-DEFICIENT MICE DEVELOP LESIONS OF ALL PHASES OF ATHEROSCLEROSIS THROUGHOUT THE ARTERIAL TREE
APOE-DEFICIENT MICE DEVELOP LESIONS OF ALL PHASES OF ATHEROSCLEROSIS THROUGHOUT THE ARTERIAL TREE
复制标题
DOI：
10.1161/01.atv.14.1.133
复制
发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
ROSS, R
中科院分区：
文献类型：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
载脂蛋白（apo）E缺陷转基因小鼠的初步描述表明，由于可能延迟清除大动脉粥样硬化颗粒从循环中严重高胆固醇血症的发展。对这些小鼠的检查表明，到10周龄时，主动脉根和肺动脉中有泡沫细胞积聚。在本研究中，动物被喂食食物或高脂肪的西式饮食，并在6至40周的年龄范围内进行检查。通过解剖显微镜进行的大体检查显示，主动脉根部、主动脉弓小弯处、主动脉的主要分支以及肺动脉和颈动脉中病变的发生倾向。在第6周（最早的检查时间点）通过光镜和电镜检查观察到单核细胞与内皮细胞的粘附。泡沫细胞病变早在8周就出现了，15周后观察到晚期病变（纤维斑块）。后者由含有平滑肌细胞的纤维帽组成，结缔组织基质包围着平滑肌细胞，结缔组织基质覆盖着大量泡沫状巨噬细胞的坏死核心。喂食西式饮食的小鼠通常比喂食普通饮食的小鼠有更严重的病变。apoE缺陷小鼠包含在动脉粥样硬化形成过程中观察到的整个病变谱，并且是第一个发展出与人类相似病变的小鼠模型。该模型为在小型遗传动物中研究动脉粥样硬化的发病机制和治疗提供了许多机会。
Initial description of apolipoprotein (apo) E-deficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clearance of large atherogenic particles from the circulation. Examination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or a high-fat, Western-type diet and examined at ages ranging from 6 to 40 weeks. Gross examination by dissection microscopy revealed a predilection for development of lesions in the aortic root, at the lesser curvature of the aortic arch, the principal branches of the aorta, and in the pulmonary and carotid arteries. Monocyte attachment to endothelial cells was observed by light and electron microscopic examination at 6 weeks, the earliest time point examined. Foam cell lesions developed as early as 8 weeks, and after 15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted of a fibrous cap containing smooth muscle cells surrounded by connective tissue matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the Western-type diet generally had more advanced lesions than those fed a chow diet. The apoE-deficient mouse contains the entire spectrum of lesions observed during atherogenesis and is the first mouse model to develop lesions similar to those in humans. This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal.