Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques

Article

关键词: SMOOTH-MUSCLE-CELLS;    MATRIX-METALLOPROTEINASE ACTIVITY;    ANEURYSM FORMATION;    TISSUE INHIBITOR;    BALLOON INJURY;    DEFICIENT MICE;    HUMAN ATHEROMA;    EXPRESSION;    MACROPHAGES;    MIGRATION;   

DOI  :  10.1161/01.CIR.0000143174.41810.10

来源: SCIE

【 摘 要 】

Background - We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques. Methods and Results - To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E - deficient mice (apoE(-/-)) that express collagenase-resistant collagen-I (Col(R/R)/ apoE(-/-), n = 12) or wild-type collagen-expressing mice (Col(+/+)/ apoE(-/-), n = 12). Aortic atheromata of both groups had similar sizes and numbers of macrophages, a major source of collagenases. However, aortic intimas from Col(R/R)/apoE(-/-) mice contained fewer smooth muscle cells, a source of collagen, probably because of decreased migration or proliferation or increased cell death. Despite reduced numbers of smooth muscle cells, atheromata of Col(R/R)/apoE(-/-) mice contained significantly more intimal collagen than did those of Col(+/+)/ apoE(-/-) mice. Conclusion - These results establish that collagenase action regulates plaque collagen turnover and smooth muscle cell accumulation.

【 授权许可】

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