Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice.
OBJECTIVE
Although it has been reported that matrix metalloproteinase (MMP)-2 is a major proteinase in atherosclerotic plaque lesions, there is no direct evidence of the role of MMP-2 in atherosclerotic lesion formation. In the present study we determined the role of MMP-2 in atherosclerosis plaque development using apolipoprotein E-deficient (apoE(-/-)) mice.


RESULTS
To generate MMP-2-deficient, apoE-deficient mice (MMP-2(-/-):apoE(-/-)), MMP-2(-/-) mice were crossed with apoE(-/-) mice. After 8 weeks of feeding with a lipid-rich diet, morphological and biochemical studies of the aortic sinus and arch were conducted. A significant reduction of the atherosclerotic plaque in the aortic sinus and arch with the decrease in smooth muscle cell-positive area was observed in MMP-2(-/-):apoE(-/-) mice compared with that of MMP-2(+/+):apoE(-/-) mice. Macrophage- and collagen-positive areas were less in aortic sinus but not in aortic arch in MMP-2(-/-):apoE(-/-) mice. There was no difference of MMP-9 mRNA expression in the plaque lesion between the 2 genotypes. A much lower level of mRNA expression of TIMP-1 and TIMP-2 was detected in the atherosclerotic plaque lesions of MMP-2(-/-):apoE(-/-) mice than in those of MMP-2(+/+):apoE(-/-) mice.


CONCLUSIONS
MMP-2 contributes to the development of atherosclerosis in apoE(-/-) mice.
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. kuzuya@med.nagoya-u.ac.jp
Masafumi
M
Kuzuya
Kae
K
Nakamura
Takeshi
T
Sasaki
Xian Wu
XW
Cheng
Shigeyoshi
S
Itohara
Akihisa
A
Iguchi
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics
D001057:Apolipoproteins E; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9