| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
We explored different expressions of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs) and plasminogen activators (PAs) in arteriosclerotic occlusive and aneurysmal diseases. Aortic samples were obtained during operation for aortic aneurysm (n=11), occlusive disease (n=10), and from fresh cadavers (n=3). We examined the expressions of MMPs, TIMPs, and PAs by zymography, western blotting and immunohistochemistry. Immunoblotting analysis showed that MMP-2 was expressed in arteriosclerotic plaque > aneurysmal wall > normal aorta, and that MMP-9 and TIMP-1 expressions were increased in aneurysmal wall compared to arteriosclerotic plaque or normal aorta. Urokinase-type PA (uPA) was expressed in arteriosclerotic plaque, but tissue-type PA (tPA) expression was increased in aneurysmal wall. Gelatin-zymograms showed that both latent and activated forms of MMP-2 were increased in arteriosclerotic plaque. Arteriosclerotic plaque had increased expression of MMP-2 in both the thickened intima and the media, and TIMP-1 and TIMP-2 expressions were increased in the intima and the media, respectively. The presence of macrophages, detected by immunohistochemistry in the adventitia of higher MMP-9 and TIMP-1 expressions in aneurysmal wall suggests that these cells are possible osurce of MMP-9 and TIMP-1. These findings suggest that the increased expressions of MMP-2 and uPA may play a role in the formation of arteriosclerotic occlusive disease, and that MMP-9, TIMP-1 and tPA expressions do in the arteriosclerotic aneurysmal formation.
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