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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1120.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effect of MMP-2 Deficiency on Atherosclerotic Lesion Formation in ApoE-Deficient Mice

Masafumi Kuzuya; Kae Nakamura; Takeshi Sasaki; Xian Wu Cheng; Shigeyoshi Itohara; Akihisa Iguchi

From the Department of Geriatrics (M.K, K.N, T.S., X.W.C., T.I., A.I.), Nagoya University Graduate School of Medicine, Japan; and RIKEN Brain Science Institute (S.I.), Saitama, Japan.

Correspondence to Masafumi Kuzuya, MD, PhD, Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail kuzuya{at}med.nagoya-u.ac.jp

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.

We determined the role of MMP-2 in atherosclerosis plaque development using the MMP-2 deficient, apolipoprotein E-deficient (MMP-2^–/–:apoE^–/–) mice. After 8 weeks of feeding with a lipid-rich diet, a significant reduction of the atherosclerotic plaque in the aortic sinus was observed in MMP-2^–/–:apoE^–/– mice compared with that of MMP-2^+/+:apoE^–/– mice.

Key Words: atherosclerosis • collagen • metalloproteinases • plaque

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