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

Dae Il Chang, Naohisa Hosomi, Jacinta Lucero, Jihoe Heo, Takeo Abumiya, Andrew P. Mazar, Gregory J. Del Zoppo

Research output: Contribution to journalArticle

108 Citations (Scopus)

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 PAI-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.

Original languageEnglish
Pages (from-to)1408-1419
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number12
DOIs
Publication statusPublished - 2003 Jan 1

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Matrix Metalloproteinase 2
Brain Ischemia
Middle Cerebral Artery Infarction
Plasminogen Activator Inhibitor 1
Tissue Plasminogen Activator
Matrix Metalloproteinase 16
Matrix Metalloproteinase 14
Papio
Urokinase-Type Plasminogen Activator
Microvessels
Basal Ganglia
Matrix Metalloproteinases
Basement Membrane
Primates
Reperfusion
In Situ Hybridization
Peptide Hydrolases
Antigens
Messenger RNA
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Chang, Dae Il ; Hosomi, Naohisa ; Lucero, Jacinta ; Heo, Jihoe ; Abumiya, Takeo ; Mazar, Andrew P. ; Del Zoppo, Gregory J. / Activation Systems for Latent Matrix Metalloproteinase-2 Are Upregulated Immediately after Focal Cerebral Ischemia. In: Journal of Cerebral Blood Flow and Metabolism. 2003 ; Vol. 23, No. 12. pp. 1408-1419.
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Activation Systems for Latent Matrix Metalloproteinase-2 Are Upregulated Immediately after Focal Cerebral Ischemia. / Chang, Dae Il; Hosomi, Naohisa; Lucero, Jacinta; Heo, Jihoe; Abumiya, Takeo; Mazar, Andrew P.; Del Zoppo, Gregory J.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 23, No. 12, 01.01.2003, p. 1408-1419.

Research output: Contribution to journalArticle

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