Activation Systems for Latent Matrix Metalloproteinase-2 Are Upregulated Immediately After Focal Cerebral Ischemia

• Published in: Journal of cerebral blood flow and metabolism Vol. 23; no. 12; pp. 1408 - 1419
• Main Authors: Chang, Dae-Il, Hosomi, Naohisa, Lucero, Jacinta, Heo, Ji-Hoe, Abumiya, Takeo, Mazar, Andrew P., del Zoppo, Gregory J.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2003; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Animals; Basal Ganglia - blood supply; Basal Ganglia - physiopathology; Biological and medical sciences; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Extracellular Matrix - metabolism; Gene Expression Regulation, Enzymologic; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - physiopathology; Male; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinases, Membrane-Associated; Medical sciences; Metalloendopeptidases - genetics; Microcirculation; Neurology; Papio; Plasminogen Activator Inhibitor 1 - genetics; Receptors, Cell Surface - genetics; Receptors, Urokinase Plasminogen Activator; Tissue Plasminogen Activator - genetics; Up-Regulation; Urokinase-Type Plasminogen Activator - metabolism; Vascular diseases and vascular malformations of the nervous system; Microvessel; Focal ischemia; Urokinase; Metalloproteinase; u-PAR; Animal model; Nervous system diseases; Pathophysiology; Enzyme; Monkey; Cardiovascular disease; Metalloendopeptidases; Cerebral disorder; Encephalon; Gelatinase A; Vascular disease; Peptidases; Vertebrata; Mammalia; Ischemia; Animal; Central nervous system disease; Primates; Hydrolases; Metalloproteinase-u-PAR-Urokinase-Microvessel-Focal ischemia; Cerebrovascular disease
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/01.WCB.0000091765.61714.30

During focal cerebral ischemia, matrix metalloproteinase-2 (MMP-2) can contribute to the loss of microvessel integrity within ischemic regions by degrading the basal lamina. MMP-2 is secreted in latent form (pro-MMP-2), but the activation of pro-MMP-2 in the ischemic territory has not been shown. Immunohistochemical and in situ hybridization studies of the expression of the direct activators of MMP-2, MT1-MMP and MT3-MMP, and the indirect activation system tissue plasminogen activator, urokinase (u-PA), its receptor (u-PAR), and its inhibitor PAI-1 after middle cerebral artery occlusion/reperfusion were undertaken in basal ganglia samples from 26 adolescent male baboons. The expressions of all three MMPs, u-PA, u-PAR, and PA1-1, but not tissue plasminogen activator, were increased from 1 hour after middle cerebral artery occlusion in the ischemic core. mRNA transcripts confirmed the increases in latent MMP-2, u-PA, u-PAR, and PAI-1 antigen very early after middle cerebral artery occlusion. The expression patterns are consistent with secretion of pro-MMP-2 and its activators in the ischemic core, perhaps from separate cell compartments. The rapid and coordinate appearance of pro-MMP-2 and its activation apparatus suggest that in the primate striatum this protease may participate in matrix injury during focal cerebral ischemia.