PERIPHERAL VASCULAR STENOSIS IN APOLIPOPROTEIN E-DEFICIENT MICE - POTENTIAL ROLES OF LIPID DEPOSITION, MEDIAL ATROPHY, AND ADVENTITIAL INFLAMMATION

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 df stenotic lesions. The arterial tree was dissected intact and included medium-sized arteries in the extremities as well as arter ies of the head and neck. The most reproducible lesions were seen in t he 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 a rtery. Consistent with what has been observed in human atherosclerotic arteries, there was dilation in response to lesion growth and no corr elation between lesion mass and lumen loss in the mouse arteries. This adaptation was especially true in the ascending aorta, where normal l umen size was maintained at atherosclerotic sites. In contrast, the ex ternal carotid arteries were stenotic in 9 of 12 animals. Here too, ho wever, loss of lumen did not correlate with lesion mass but did correl ate 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 t he stenotic process in advanced atherosclerotic vessels may depend on death of medial smooth muscle cells. possibly in response to inflammat ory changes in plaque or adventitia.