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

JO Deguchi, E Aikawa, P Libby, JR Vachon, M Inada… - Circulation, 2005 - Am Heart Assoc
JO Deguchi, E Aikawa, P Libby, JR Vachon, M Inada, SM Krane, P Whittaker, M Aikawa
Circulation, 2005Am Heart Assoc
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 …
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<0.01). 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.
Am Heart Assoc