Matrix Metalloproteinase Expressions in Arteriosclerosis

探讨基质金属蛋白酶(MMPs)、金属蛋白酶组织抑制物(TIMPs)和纤溶酶原激活物(PAS)在动脉硬化性闭塞症和动脉瘤性疾病中的不同表达。主动脉瘤11例，闭塞症10例，新鲜身体3例。用酶谱、免疫印迹和免疫组织化学方法检测MMPs、TIMPs和PAS的表达。免疫印迹分析显示，基质金属蛋白酶-2在动脉硬化斑块和正常主动脉中均有表达，而在动脉瘤壁中的表达高于动脉硬化斑块和正常主动脉。尿激酶型纤溶酶原激活物(UPA)在动脉粥样硬化斑块中表达，而组织型纤溶酶原激活物(TPA)在动脉瘤壁上表达增加。明胶酶谱显示动脉粥样硬化斑块中潜伏期和激活期的基质金属蛋白酶-2均增加。动脉粥样硬化斑块增厚的内膜和中膜均有基质金属蛋白酶-2的表达增加，TIMP-1和TIMP-2的表达分别在内膜和中膜增加。免疫组织化学检测发现，在动脉瘤壁高表达的外膜中有巨噬细胞的存在，提示这些细胞可能是MMP-9和TIMP-1的来源。提示MMP2和uPA的高表达可能在动脉硬化性闭塞症的形成中起一定作用，而MMP9、TIMP 1和tPA的表达在动脉硬化性动脉瘤的形成中起一定作用。

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.