MATRIX METALLOPROTEINASE-9 IN CEREBRAL ANEURYSMS

OBJECTIVE: Generalized disruption of arterial wall morphological chang es in patients harboring cerebral aneurysms has been documented; howev er, little is known regarding the pathogenesis of these changes. To ex plore the role of the elastolytic gelatinase, matrix metalloproteinase -9 (MMP-9), levels of this enzyme in the wall of intracranial aneurysm s were compared with those in both intracranial and extracranial arter ies. The tissue levels of its major inhibitor, tissue inhibitor of met alloproteinase (TIMP), were measured in these tissues as well. The act ivity of MMP-9 in plasma was also evaluated, METHODS: The aneurysm wal l was excised from three of six patients undergoing craniotomies for a neurysm 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 craniotomie s for nonvascular disease. An intracranial artery was also obtained fr om the anterior temporal neocortical resection of a patient undergoing a craniotomy for mesial temporal sclerosis. MMP-9 and TIMP levels wer e determined via Western blot analysis. Using substrate gel zymography , MMP-9 plasma activity was determined for a separate cohort of patien ts with aneurysms (n = 6) and patients in the control group (n = 6). R ESULTS: MMP-9 and TIMP levels in the aneurysm wall were markedly incre ased beyond levels in both extracranial arteries (STAs from patients w ith aneurysms and patients in the control group) and the intracranial artery. There were no differences in the levels of MMP-9 in the STAs o f patients harboring aneurysms when compared with patients in the cont rol group. Also, no differences were noted in plasma MMP-9 activity. C ONCLUSION: Local rather than systemic perturbations in MMP-9 levels ma y contribute to the matrix disruption associated with cerebral aneurys ms. 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 presymptomati c aneurysms. However, local therapeutic modulation of MMP-9 activity m ay help arrest aneurysm progression.