Peripheral vascular stenosis in apolipoprotein e-deficient mice: Potential roles of lipid deposition, medial atrophy, and adventitial inflammation

Hong Seog Seo, Donna M. Lombardi, Patti Polinsky, Lyn Powell-Braxton, Stuart Bunting, Stephen M. Schwartz, Michael E. Rosenfeld

    Research output: Contribution to journalArticlepeer-review

    75 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)3593-3601
    Number of pages9
    JournalArteriosclerosis, thrombosis, and vascular biology
    Volume17
    Issue number12
    DOIs
    Publication statusPublished - 1997

    Keywords

    • Adventitial inflammation
    • Apolipoprotein E
    • Compensatory remodeling
    • Medial necrosis
    • Stenosis

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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