Atherosclerotic lesions in the common coronary arteries of ApoE knockout mice

Objective: The present study describes the distribution of atherosclerotic lesions in the coronary arteries of chow-fed 60-week-old male ApoE(-/-), 17-beta-estradiol-treated ApoE(-/-), and wild-type mice. Methods and results: The histologic examination of coronary arteries in 12 ApoE(-/-) and 6 wild-type mice, in contrast to the distribution of atherosclerosis in human coronary arteries, reveals that the major lesions in the mouse are located in the valve sinus, including the origins of the coronary arteries. These retrovalvular lesions either stop abruptly at the orifice of the common coronary artery or extend a short distance onto the arterial trunks. The first segment and first branch of all the major coronary arteries, the usual sites of disease in humans, are protected from disease. Although the arterial trunks and the first level branches are free of disease, we found approximately four independent lesions per heart. Independent lesions are present in the heart in smaller, intramyocardial vessels. These lesions are comprised predominantly of macrophages and proteoglycan and exhibit little extracellular lipid. In some cases, the independent lesions occlude the lumen without evidence of myocardial infarct in the surrounding tissue. Conclusions: The specificity of the localization of lesions in certain segments of the murine coronary tree suggests that fundamental properties found at different branch levels determine lesion location. (c) 2005 Published by Elsevier Inc.