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.