Effect of MMP-2 deficiency on atherosclerotic lesion formation in ApoE-deficient mice
Effect of MMP-2 deficiency on atherosclerotic lesion formation in ApoE-deficient mice
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DOI：
10.1161/01.atv.0000218496.60097.e0
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发表时间：
2006-05-01
影响因子：
8.7
通讯作者：
Iguchi, A
中科院分区：
文献类型：
--
作者：
Kuzuya, M;Nakamura, K;Iguchi, A
目的：尽管已有报道基质金属蛋白酶（MMP）- 2是动脉粥样硬化斑块病变中的主要蛋白酶，但没有直接证据表明MMP-2在动脉粥样硬化病变形成中的作用。方法和结果-为了产生MMP-2缺陷型、apoE缺陷型小鼠（MMP-2（-/-）：apoE（-/-）），将MMP-2（-/-）小鼠与apoE（-/-）小鼠杂交。在用富含脂质的饮食喂养8周后，进行主动脉窦和弓的形态学和生化研究。与MMP-2（+/+）：apoE（-/-）小鼠相比，MMP-2（-/-）：apoE（-/-）小鼠主动脉窦和主动脉弓中的动脉粥样硬化斑块显著减少，平滑肌细胞阳性面积减少。MMP-2（-/-）：apoE（-/-）小鼠的主动脉窦中巨噬细胞和胶原蛋白阳性区域较少，而主动脉弓中则无。两种基因型间斑块中MMP-9 mRNA表达无差异。MMP-2（-/-）：apoE（-/-）小鼠动脉粥样硬化斑块中TIMP-1和TIMP-2 mRNA表达水平明显低于MMP-2（+/+）：apoE（-/-）小鼠。
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.