Matrix metalloproteinase-9 in cerebral aneurysms
Matrix metalloproteinase-9 in cerebral aneurysms
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DOI：
10.1097/00006123-199709000-00027
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发表时间：
1997-09-01
期刊：
影响因子：
4.8
通讯作者：
Connolly, ES
中科院分区：
文献类型：
--
作者：
Kim, SC;Singh, M;Connolly, ES
目的：已经记录了患有脑动脉瘤的患者的动脉壁形态变化的普遍破坏;然而，关于这些变化的发病机制知之甚少。为探讨基质金属蛋白酶-9（MMP-9）在颅内动脉瘤中的作用，将颅内动脉瘤壁中MMP-9的含量与颅内外动脉瘤壁中MMP-9的含量进行比较。在这些组织中也测量其主要抑制剂金属蛋白酶组织抑制剂（TIMP）的组织水平。方法：对6例颅内动脉瘤患者行开颅夹闭术，其中3例切除动脉瘤壁，测定血浆MMP-9活性。从6例患者中的每一个中获得了一段1cm的颞浅动脉（STA），从对照组中的6例患者中获得了额外的STA，这些患者因非血管性疾病而接受开颅手术。一个颅内动脉也获得了从前颞新皮质切除的病人接受开颅手术的内侧颞硬化。MMP-9和TIMP水平通过蛋白质印迹分析测定。使用底物凝胶酶谱法，MMP-9的血浆活性测定一个单独的队列的患者与动脉瘤（n = 6）和患者在对照组（n = 6）。结果：MMP-9和TIMP的水平在动脉瘤壁显着增加超过水平在颅外动脉（STA从动脉瘤患者和对照组患者）和颅内动脉。与对照组相比，患有动脉瘤的患者的STA中MMP-9的水平没有差异。此外，血浆MMP-9 activity.CONCLUSION：局部而不是全身的MMP-9水平的扰动可能有助于与脑动脉瘤基质破坏。这种局部上调不是TIMP下调的结果。缺乏增加的全身金属蛋白酶活性排除了使用血浆MMP-9活性作为症状前动脉瘤的筛查工具。然而，MMP-9活性的局部治疗调节可能有助于阻止动脉瘤进展。
OBJECTIVE: Generalized disruption of arterial wall morphological changes in patients harboring cerebral aneurysms has been documented; however, little is known regarding the pathogenesis of these changes. To explore the role of the elastolytic gelatinase, matrix metalloproteinase-9 (MMP-9), levels of this enzyme in the wall of intracranial aneurysms were compared with those in both intracranial and extracranial arteries. The tissue levels of its major inhibitor, tissue inhibitor of metalloproteinase (TIMP), were measured in these tissues as well. The activity of MMP-9 in plasma was also evaluated,METHODS: The aneurysm wall was excised from three of six patients undergoing craniotomies for aneurysm clipping. A l-cm segment of superficial temporal artery (STA) was obtained from each of six patients, Additional STAs were obtained from six patients in the control group who were undergoing craniotomies for nonvascular disease. An intracranial artery was also obtained from the anterior temporal neocortical resection of a patient undergoing a craniotomy for mesial temporal sclerosis. MMP-9 and TIMP levels were determined via Western blot analysis. Using substrate gel zymography, MMP-9 plasma activity was determined for a separate cohort of patients with aneurysms (n = 6) and patients in the control group (n = 6).RESULTS: MMP-9 and TIMP levels in the aneurysm wall were markedly increased beyond levels in both extracranial arteries (STAs from patients with aneurysms and patients in the control group) and the intracranial artery. There were no differences in the levels of MMP-9 in the STAs of patients harboring aneurysms when compared with patients in the control group. Also, no differences were noted in plasma MMP-9 activity.CONCLUSION: Local rather than systemic perturbations in MMP-9 levels may contribute to the matrix disruption associated with cerebral aneurysms. This local up-regulation is not the result of TIMP down-regulation. The lack of increased systemic metalloproteinase activity precludes the use of plasma MMP-9 activity as a screening fool for presymptomatic aneurysms. However, local therapeutic modulation of MMP-9 activity may help arrest aneurysm progression.