Matrix Metalloproteinase-13/Collagenase-3 Deletion Promotes Collagen Accumulation and Organization in Mouse Atherosclerotic Plaques

Abstract
Background— Interstitial collagen plays a crucial structural role in arteries. Matrix metalloproteinases (MMPs), including MMP-13/collagenase-3, likely contribute to collagen catabolism in atherosclerotic plaques. Methods and Results— To test the hypothesis that a specific MMP-collagenase influences the development and structure of atherosclerotic plaques, this study used atherosclerosis-susceptible apolipoprotein E–deficient mice that lack MMP-13/collagenase-3 (Mmp-13−/−/apoE−/−) or express wild-type MMP-13/collagenase-3 (Mmp-13+/+/apoE−/−). Both groups consumed an atherogenic diet for 5 (n=8) or 10 weeks (n=9). Histological analyses of the aortic root of both groups revealed similar plaque size and accumulation of smooth muscle cells (a collagen-producing cell type) and macrophages (a major source of plaque collagenases) after 5 and 10 weeks of atherogenic diet. By 10 weeks, the plaques of Mmp-13−/−/apoE−/− mice contained significantly more interstitial collagen than those of Mmp-13+/+/apoE−/− mice (P<0...

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