Difference in matrix-degrading protease expression and activity between thrombus-free and thrombus-covered wall of abdominal aortic aneurysm
Difference in matrix-degrading protease expression and activity between thrombus-free and thrombus-covered wall of abdominal aortic aneurysm
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DOI：
10.1161/01.atv.0000166601.49954.21
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发表时间：
2005-07-01
影响因子：
8.7
通讯作者：
Eriksson, P
中科院分区：
文献类型：
--
作者：
Kazi, M;Zhu, CY;Eriksson, P
目的：腹主动脉瘤腔内血栓是腹主动脉瘤破裂的易感因素。在这里，我们研究了腔内血栓影响腹主动脉壁基质降解酶的表达和活性的可能性。方法和结果-20例接受腹主动脉选择性修补术的患者。从每个患者的血栓覆盖和无血栓的壁上取标本进行分析。基因芯片和实时定量聚合酶链式反应显示基质金属蛋白酶-1、-7、-9和-12在无血栓壁上的表达较有血栓覆盖的壁上表达上调。免疫组织化学证实了基质金属蛋白酶-9的差异表达，但也将基质金属蛋白酶-9定位于血栓和潜在血管壁之间的交界处。基质金属蛋白酶-9表达与巨噬细胞共存。尿激酶型纤溶酶原激活物(UPA)、uPA受体和纤溶酶原激活物抑制物-1的表达模式相似。明胶酶的活性与基质金属蛋白酶-9蛋白表达的区域相同，即在无血栓的壁上和在血栓与下壁间的交界处。结论：本工作表明，在动脉瘤壁内，明胶酶的表达和活性有所不同。需要进一步确定导致血栓覆盖的壁降解的蛋白水解酶的来源和活性。
Objective-It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA rupture. Here, we examined the possibility that the intraluminal thrombus influences expression and activity of matrix-degrading proteases in the AAA wall.Methods and Results-Twenty patients undergoing elective repair of AAAs were included. From each patient, specimens from both thrombus-covered and thrombus-free wall were taken for analysis. Gene arrays and quantitative real-time polymerase chain reaction showed that matrix metalloproteinase (MMP)-1, -7, -9, and -12 expressions were upregulated in the thrombus-free wall compared with the thrombus-covered wall. Immunohistochemistry confirmed the differential expression of MMP-9 but also localized MMP-9 to the interface between the thrombus and the underlying vessel wall. MMP-9 expression was colocalized with the presence of macrophages. Similar expression patterns were observed for urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-1. Gelatinase activity was detected in the same regions as MMP-9 protein expression, ie, within the thrombus-free wall and in the interface between the thrombus and the underlying wall.Conclusion-The present work demonstrates that protease expression and activity differs within the aneurysm wall. The source and activity of the proteases responsible for the degradation of the thrombus-covered wall need to be further determined.