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Arterioscler Thromb Vasc Biol. 2006 May;26(5):1120-5. Epub 2006 Mar 23.

Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice.

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1
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. kuzuya@med.nagoya-u.ac.jp

Abstract

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.

METHODS AND 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.

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