Matrix Metalloproteinase Expressions in Arteriosclerosis

我们探讨了基质金属蛋白酶（MMPs）、金属蛋白酶组织抑制剂（TIMPs）和纤溶酶原激活剂（PAs）在动脉硬化性闭塞和动脉瘤性疾病中的不同表达。主动脉样本采集于主动脉瘤（n=11）、闭塞性疾病（n=10）和新鲜尸体（n=3）的手术中。我们通过酶谱、western blotting和免疫组织化学检测MMPs、TIMPs和PAs的表达。免疫印迹分析显示，MMP-2在动脉硬化斑块>、动脉瘤壁>正常主动脉中表达，MMP-9和TIMP-1在动脉瘤壁中的表达较动脉硬化斑块和正常主动脉明显增加。尿激酶型PA （uPA）在动脉硬化斑块中表达，而组织型PA （tPA）在动脉瘤壁中表达增加。明胶酶谱显示MMP-2的潜伏和活化形式在动脉硬化斑块中均增加。动脉硬化斑块增厚的内膜和中膜中MMP-2表达升高，内膜和中膜中TIMP-1和TIMP-2表达升高。免疫组化检测发现，在MMP-9和TIMP-1表达较高的动脉瘤壁外膜中存在巨噬细胞，提示这些细胞可能是MMP-9和TIMP-1的来源。这些结果提示，MMP-2和uPA表达升高可能参与动脉硬化性闭塞疾病的形成，MMP-9、TIMP-1和tPA表达升高可能参与动脉硬化性动脉瘤的形成。

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.