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. 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.