Activation systems for latent matrix metalloproteinase-2 are upregulated immediately after focal cerebral ischemia.

Abstract

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.

• Authors: Dae-Il Chang, Naohisa Hosomi, Jacinta Lucero, Ji-Hoe Heo, Takeo Abumiya, Andrew P Mazar, Gregory J del Zoppo
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 23 Issue 12 Pg. 1408-19 (Dec 2003) ISSN: 0271-678X [Print] United States
• PMID: 14663336 (Publication Type: Journal Article)

Chemical References

• Plasminogen Activator Inhibitor 1
• Receptors, Cell Surface
• Receptors, Urokinase Plasminogen Activator
• Tissue Plasminogen Activator
• Urokinase-Type Plasminogen Activator
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases
• Matrix Metalloproteinase 2

Topics

• Animals
• Basal Ganglia (blood supply, physiopathology)
• Brain Ischemia (metabolism, physiopathology)
• Extracellular Matrix (metabolism)
• Gene Expression Regulation, Enzymologic
• Infarction, Middle Cerebral Artery (metabolism, physiopathology)
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases (genetics)
• Microcirculation
• 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)