Genetically Determined Resistance to Collagenase Action Augments Interstitial Collagen Accumulation in Atherosclerotic Plaques
- 5 October 2004
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 110 (14) , 1953-1959
- https://doi.org/10.1161/01.cir.0000143174.41810.10
Abstract
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 (ColR/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 ColR/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 mu...Keywords
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