ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.

TLDR

Severe hypercholesterolemia in apoE‑deficient transgenic mice arises from delayed clearance of large atherogenic particles. The model is intended to enable detailed study of atherosclerosis pathogenesis and therapy in a small, genetically defined animal. Mice were fed chow or a high‑fat Western diet and examined from 6 to 40 weeks of age. The apoE‑deficient mouse develops a full spectrum of atherosclerotic lesions—foam cells by 8 weeks, monocyte adhesion at 6 weeks, fibrous plaques with necrotic cores after 15 weeks, and a predilection for the aortic root, arch, branches, pulmonary and carotid arteries—whose severity is greater on a Western diet, mirroring human disease.

Abstract

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.