From the Cerebrovascular Research Laboratory, Section of Cerebrovascular
Surgery, Department of Neurosurgery, The Cleveland Clinic Foundation (Ohio).
Correspondence to Douglas Chyatte, MD, Section of Cerebrovascular Surgery, Department of Neurosurgery–S80, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail chyattd{at}cesmtp.ccf.org
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 (n=60). Pretreatment
of the serum by APMA (n=60) lowered the molecular weight of the band to
66 kDa. The band was inhibited by EDTA (n=10) but not PMSF (n=10), thus
characterizing the circulating 72-kDa gelatinase as an inactive
pro-MMP. Western blotting (n=20) 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.
© 1998 American Heart Association, Inc.
Original Contributions
Identification of a Serum Gelatinase Associated With the Occurrence of Cerebral Aneurysms as Pro-Matrix Metalloproteinase-2
Key Words: cerebral aneurysm • gelatinases • metalloproteinases
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