VASCULAR EXTRACELLULAR-MATRIX REMODELING IN CEREBRAL ANEURYSMS

Object. The occurrence of cerebral aneurysms has been linked to altera tions in the extracellular matrix and to matrix-degrading proteases. T he purpose of the present study was to determine whether active extrac ellular matrix remodeling occurs within cerebral aneurysms. Methods. A neurysm tissue was collected from 23 patients (two of whom had a ruptu red aneurysm and 21 of whom had an unruptured aneurysm) and compared w ith ii control basilar arteries harvested at autopsy. Active proteinas es capable of gelatin lysis were identified by performing in situ zymo graphy in the presence and absence of a metalloproteinase inhibitor (e thylenediamine tetraacetic acid) and a serine proteinase inhibitor (ph enylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)-plasminogen activator (PA), urokina se-type (u)-PA, membranetype (MT1)-matrix metalloproteinase (MMP), MMP -2, MMP-9, and tenascin. Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control ar teries (two of 11) (p = 0.002). Both serine proteinases and MMPs contr ibuted to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in t he aneurysm tissue but were unusual in control tissue. The MMP-2 was a lso expressed more commonly in aneurysm than in control tissue (p = 0. 07). The MMP-9 and t-PA were expressed in both groups; however, differ ent staining patterns were observed between aneurysm and control tissu e. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present. Conclusions. Aneurysm tissue demonstrate s increased proteolytic activity capable of lysing gelatin and increas ed expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm fo rmation and growth.