Matrix Metalloproteinase Expressions in Arteriosclerosis

动脉硬化中基质金属蛋白酶的表达

• 批准号: 07671308
• 负责人: ZEMPO Nobuya
• 金额: $ 1.54万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671308/
• 关键词: Arteriosclerosis; intimal hyperplasia; Aneurysm; matrix metalloproteinase; tissue inhibitor of metalloproteinase

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.

探讨基质金属蛋白酶（MMPs）、金属蛋白酶组织抑制剂（TIMPs）和纤溶酶原激活物（PAs）在动脉闭塞性疾病和动脉瘤性疾病中的表达差异。主动脉样本在主动脉瘤（n=11）、闭塞性疾病（n=10）和新鲜尸体（n=3）手术期间获得。采用酶谱法、免疫印迹法和免疫组化法检测MMPs、TIMPs和PAs的表达。免疫印迹分析显示，MMP-2在动脉粥样硬化斑块中的表达高于动脉瘤壁，而MMP-9和TIMP-1在动脉瘤壁中的表达高于动脉粥样硬化斑块和正常主动脉。尿激酶型PA（uPA）在动脉粥样硬化斑块中表达，而组织型PA（tPA）在动脉粥样硬化壁中表达增强。明胶酶谱显示，动脉粥样硬化斑块中MMP-2的潜伏型和活化型均增加。动脉粥样硬化斑块中MMP-2在增厚的内膜和中膜表达增加，TIMP-1和TIMP-2在内膜和中膜表达分别增加。免疫组化显示巨噬细胞存在于MMP-9和TIMP-1高表达的血管外膜中，提示这些细胞可能是MMP-9和TIMP-1的来源。提示MMP-2、uPA表达增高可能参与了动脉闭塞性病变的形成，MMP-9、TIMP-1、tPA表达增高可能参与了动脉闭塞性病变的形成。