Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased 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 formation and growth.

Background and Purpose-Subarachnoid hemorrhage from intracranial aneurysm rupture produces a severe form of stroke. Extracellular matrix remodeling is associated with cerebral aneurysms and may play a role in the formation or rupture of these lesions. We previously reported a 3-fold increase in a 72-kDa serum gelatinase in a subgroup of aneurysm patients. The purpose of the present study was to further characterize and identify this gelatinase. Methods-Serum samples were collected from surgical patients with intracranial aneurysms. The following series of experiments was designed to further characterize and identify the predominant serum gelatinase found in the subgroup of patients with increased gelatinase activity. Gelatin zymography was performed on native serum samples and compared with serum that had been pretreated with a known metalloproteinase activator (4-aminophenylmercuric acetate [APMA]). Gelatin zymography was repeated in the presence of a matrix metalloproteinase (MMP) inhibitor (EDTA) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride [PMSF]). Final identification was made by Western blotting with the use of monoclonal antibodies to MMP-2 and MMP-9. Results-A consistent gelatinolytic band (72 kDa) was identified in all serum samples (nϭ60). Pretreatment of the serum by APMA (nϭ60) lowered the molecular weight of the band to 66 kDa. The band was inhibited by EDTA (nϭ10) but not PMSF (nϭ10), thus characterizing the circulating 72-kDa gelatinase as an inactive pro-MMP. Western blotting (nϭ20) identified the 72-kDa band as MMP-2. Conclusions-These findings confirm that the increased gelatinolytic activity observed in vitro in a subset of cerebral aneurysm patients is due to pro-MMP-2. (Stroke. 1998;29:1580-1583.)Key Words: cerebral aneurysm Ⅲ gelatinases Ⅲ metalloproteinases C erebral aneurysms usually remain asymptomatic until rupture occurs. Despite modern therapy, aneurysmal subarachnoid hemorrhage remains one of the most severe forms of cerebrovascular disease, with a mortality approaching 50%. [1][2][3][4][5][6] Understanding the biology of cerebral aneurysms may lead to new therapeutic strategies for these extremely ill patients.Previous work by this laboratory has found a 3-fold increase in a 72-kDa serum gelatinase in a subgroup of aneurysm patients. In that study, aneurysm patients (52% ruptured, 48% unruptured) were compared with surgical patients known to be free of cerebral aneurysms. One half of the aneurysm patients had a 3-fold increase in serum gelatinase activity as measured by quantitative gelatin zymography compared with the controls. This increased activity was irrespective of their hemorrhage status.7 Vascular extracellular matrix (ECM) remodeling is known to be orchestrated and regulated by a complex network of proteases and protease inhibitors.8 -10 Molecular markers of matrix remodeling have been found in both cerebral and aortic aneurysm patients. 7,11 The purpose of the present study was to further characterize and identify this circulating gelatinase.The famili...

These findings are consistent with the hypothesis that accelerated enzymatic degradation of collagens and other structural proteins compromises the mechanical integrity of the cerebral vessel wall and leads to conditions that favor aneurysm formation.

Observations of the planets made at the Mt. Wilson Observatory during the past year have led to the surprising conclusion that Mercury, the smallest of the planets and the one nearest the sun, turns on its axis rapidly and not in a period of 88 days, equal to that of its revolution around the sun, as has long been believed. perpendicular to its orbit. The temperature at any one point on the planet^s surface would be uniform throughout the year, intensely hot in equatorial regions, frigid in polar regions, though air currents would do much toward equalizing the extremes of heat and cold.

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