Matrix metalloproteinase-13/collagenase-3 deletion promotes collagen accumulation and organization in mouse atherosclerotic plaques

Background-Interstitial collagen plays a crucial structural role in arteries. Matrix metalloproteinases ( MMPs), includingMMP-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 < 0.01). Furthermore, quantitative optical analyses revealed thinner and less aligned periluminal collagen fibers within the plaques of Mmp-13(-/-)/ apoE(-/-) mice versus those from Mmp-13(+/+)/apoE(-/-) mice. Conclusions-These data support the hypothesis that MMP-13/collagenase- 3 plays a vital role in the regulation and organization of collagen in atherosclerotic plaques.