APOE-DEFICIENT MICE DEVELOP LESIONS OF ALL PHASES OF ATHEROSCLEROSIS THROUGHOUT THE ARTERIAL TREE

被引:1417
作者
NAKASHIMA, Y
PLUMP, AS
RAINES, EW
BRESLOW, JL
ROSS, R
机构
[1] UNIV WASHINGTON, DEPT PATHOL, SEATTLE, WA 98195 USA
[2] ROCKEFELLER UNIV, BIOCHEM GENET & METAB LAB, NEW YORK, NY 10021 USA
来源
ARTERIOSCLEROSIS AND THROMBOSIS | 1994年 / 14卷 / 01期
关键词
ATHEROSCLEROSIS; APOLIPOPROTEIN E; TRANSGENIC MOUSE MODEL; LESIONS OF ATHEROSCLEROSIS;
D O I
10.1161/01.ATV.14.1.133
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:133 / 140
页数:8
相关论文
共 27 条
[21]   THE PATHOGENESIS OF ATHEROSCLEROSIS - A PERSPECTIVE FOR THE 1990S [J].
ROSS, R .
NATURE, 1993, 362 (6423) :801-809
[22]  
Schwartz C J, 1985, Virchows Arch A Pathol Anat Histopathol, V405, P175, DOI 10.1007/BF00704370
[23]  
SIMA A, 1990, J SUBMICR CYTOL PATH, V22, P1
[25]   DEVELOPMENT OF PIGEON STRAINS WITH SELECTED ATHEROSCLEROSIS CHARACTERISTICS [J].
WAGNER, WD ;
CLARKSON, TB ;
FELDNER, MA ;
PRICHARD, RW .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 1973, 19 (03) :304-319
[26]   ATHEROSCLEROSIS IN TRANSGENIC MICE OVEREXPRESSING APOLIPOPROTEIN-A-II [J].
WARDEN, CH ;
HEDRICK, CC ;
QIAO, JH ;
CASTELLANI, LW ;
LUSIS, AJ .
SCIENCE, 1993, 261 (5120) :469-472
[27]   SPONTANEOUS HYPERCHOLESTEROLEMIA AND ARTERIAL LESIONS IN MICE LACKING APOLIPOPROTEIN-E [J].
ZHANG, SH ;
REDDICK, RL ;
PIEDRAHITA, JA ;
MAEDA, N .
SCIENCE, 1992, 258 (5081) :468-471