Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3593-3601
© 1997 American Heart Association, Inc.
Articles |
Peripheral Vascular Stenosis in Apolipoprotein E-Deficient Mice
Potential Roles of Lipid Deposition, Medial Atrophy, and Adventitial Inflammation
From the Departments of Pathology (H.S.S., D.M.L., P.P., S.M.S., M.E.R.) and Pathobiology (M.E.R.), University of Washington, Seattle, Wash, and the Cardiovascular Research Department, Genentech, Inc, South San Francisco, Calif (L.P-B., S.B.)
Correspondence to Michael E. Rosenfeld, Department of Pathobiology, Box 353410, University of Washington, Seattle, WA 98195. E-mail ssmjm{at}u.washington.edu
Abstract A systematic analysis of the distribution of advanced atherosclerotic lesions was undertaken in chow-fed, 9-month-old apolipoprotein (apo) E-deficient mice to identify sites amenable for study of mechanisms of formation of stenotic lesions. The arterial tree was dissected intact and included medium-sized arteries in the extremities as well as arteries of the head and neck. The most reproducible lesions were seen in the ascending aorta and in the carotid, femoral, and popliteal arteries. Casting of the vascular tree provided additional verification of the presence of lumen narrowing in the external branches of the carotid artery. Consistent with what has been observed in human atherosclerotic arteries, there was dilation in response to lesion growth and no correlation between lesion mass and lumen loss in the mouse arteries. This adaptation was especially true in the ascending aorta, where normal lumen size was maintained at atherosclerotic sites. In contrast, the external carotid arteries were stenotic in 9 of 12 animals. Here too, however, loss of lumen did not correlate with lesion mass but did correlate with adventitial inflammation and medial atrophy. Lumen narrowing also occurred most frequently at sites where extracellular cholesterol clefts were a prominent part of the lesion. These data suggest that the stenotic process in advanced atherosclerotic vessels may depend on death of medial smooth muscle cells, possibly in response to inflammatory changes in the plaque or adventitia.
Key Words: stenosis • compensatory remodeling • medial necrosis • adventitial inflammation • apolipoprotein E
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