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), including MMP-13/collagenase-3, likely contribute to collagen catabolism in atherosclerotic plaques.


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.
Deguchi
Jun-O
JO
Donald W. Reynolds Cardiovascular Clinical Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Aikawa
Elena
E
Libby
Peter
P
Vachon
Jeffrey R
JR
Inada
Masaki
M
Krane
Stephen M
SM
Whittaker
Peter
P
Aikawa
Masanori
M
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000172:deficiency*; D004036:Diet, Atherogenic; D017353:Gene Deletion; D053509:Matrix Metalloproteinase 13; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse