Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion

Naohisa Hosomi, Jacinta Lucero, Ji Hoe Heo, James A. Koziol, Brian R. Copeland, Gregory J. Del Zoppo

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Background and Purpose - During focal cerebral ischemia, the microvascular matrix (ECM), which participates in microvascular integrity, is degraded and lost when neurons are injured. Loss of microvascular basal lamina antigens coincides with rapid expression of select matrix metalloproteinases (MMPs). Plasminogen activators (PAs) may also play a role in ECM degradation by the generation of plasmin or by MMP activation. Methods - The endogenous expressions of tissue-type plasminogen activator (tPA), urokinase (uPA), and PA inhibitor-1 (PAI-1) were quantified in 10-μm frozen sections from ischemic and matched nonischemic basal ganglia and in the plasma of 34 male healthy nonhuman primates before and after middle cerebral artery occlusion (MCA:O). Results - Within the ischemic basal ganglia, tissue uPA activity and antigen increased significantly within 1 hour after MCA:O (2P<0.005). tPA activity transiently decreased 2 hours after MCA:O (2P=0.01) in concert with an increase in PAI-1 antigen (2P=0.001) but otherwise did not change. The transient decrease in free tPA antigen was marked by an increase in the tPA-PAI-1 complex (2P<0.001). No significant relations to neuronal injury or intracerebral hemorrhage were discerned. Conclusions - The rapid increase in endogenous PA activity is mainly due to significant increases in uPA, but not tPA, within the ischemic basal ganglia after MCA:O. This increase and an increase in PAI-1 coincided with latent MMP-2 generation and microvascular ECM degeneration but not neuronal injury.

Original languageEnglish
Pages (from-to)1341-1348
Number of pages8
JournalStroke
Volume32
Issue number6
DOIs
Publication statusPublished - 2001 Jan 1

Fingerprint

Plasminogen Activators
Middle Cerebral Artery Infarction
Basal Ganglia
Antigens
Plasminogen Activator Inhibitor 1
Matrix Metalloproteinases
Fibrinolysin
Matrix Metalloproteinase 2
Urokinase-Type Plasminogen Activator
Cerebral Hemorrhage
Wounds and Injuries
Frozen Sections
Tissue Plasminogen Activator
Brain Ischemia
Basement Membrane
Primates
Neurons

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Hosomi, Naohisa ; Lucero, Jacinta ; Heo, Ji Hoe ; Koziol, James A. ; Copeland, Brian R. ; Del Zoppo, Gregory J. / Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion. In: Stroke. 2001 ; Vol. 32, No. 6. pp. 1341-1348.
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Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion. / Hosomi, Naohisa; Lucero, Jacinta; Heo, Ji Hoe; Koziol, James A.; Copeland, Brian R.; Del Zoppo, Gregory J.

In: Stroke, Vol. 32, No. 6, 01.01.2001, p. 1341-1348.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion

AU - Hosomi, Naohisa

AU - Lucero, Jacinta

AU - Heo, Ji Hoe

AU - Koziol, James A.

AU - Copeland, Brian R.

AU - Del Zoppo, Gregory J.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Background and Purpose - During focal cerebral ischemia, the microvascular matrix (ECM), which participates in microvascular integrity, is degraded and lost when neurons are injured. Loss of microvascular basal lamina antigens coincides with rapid expression of select matrix metalloproteinases (MMPs). Plasminogen activators (PAs) may also play a role in ECM degradation by the generation of plasmin or by MMP activation. Methods - The endogenous expressions of tissue-type plasminogen activator (tPA), urokinase (uPA), and PA inhibitor-1 (PAI-1) were quantified in 10-μm frozen sections from ischemic and matched nonischemic basal ganglia and in the plasma of 34 male healthy nonhuman primates before and after middle cerebral artery occlusion (MCA:O). Results - Within the ischemic basal ganglia, tissue uPA activity and antigen increased significantly within 1 hour after MCA:O (2P<0.005). tPA activity transiently decreased 2 hours after MCA:O (2P=0.01) in concert with an increase in PAI-1 antigen (2P=0.001) but otherwise did not change. The transient decrease in free tPA antigen was marked by an increase in the tPA-PAI-1 complex (2P<0.001). No significant relations to neuronal injury or intracerebral hemorrhage were discerned. Conclusions - The rapid increase in endogenous PA activity is mainly due to significant increases in uPA, but not tPA, within the ischemic basal ganglia after MCA:O. This increase and an increase in PAI-1 coincided with latent MMP-2 generation and microvascular ECM degeneration but not neuronal injury.

AB - Background and Purpose - During focal cerebral ischemia, the microvascular matrix (ECM), which participates in microvascular integrity, is degraded and lost when neurons are injured. Loss of microvascular basal lamina antigens coincides with rapid expression of select matrix metalloproteinases (MMPs). Plasminogen activators (PAs) may also play a role in ECM degradation by the generation of plasmin or by MMP activation. Methods - The endogenous expressions of tissue-type plasminogen activator (tPA), urokinase (uPA), and PA inhibitor-1 (PAI-1) were quantified in 10-μm frozen sections from ischemic and matched nonischemic basal ganglia and in the plasma of 34 male healthy nonhuman primates before and after middle cerebral artery occlusion (MCA:O). Results - Within the ischemic basal ganglia, tissue uPA activity and antigen increased significantly within 1 hour after MCA:O (2P<0.005). tPA activity transiently decreased 2 hours after MCA:O (2P=0.01) in concert with an increase in PAI-1 antigen (2P=0.001) but otherwise did not change. The transient decrease in free tPA antigen was marked by an increase in the tPA-PAI-1 complex (2P<0.001). No significant relations to neuronal injury or intracerebral hemorrhage were discerned. Conclusions - The rapid increase in endogenous PA activity is mainly due to significant increases in uPA, but not tPA, within the ischemic basal ganglia after MCA:O. This increase and an increase in PAI-1 coincided with latent MMP-2 generation and microvascular ECM degeneration but not neuronal injury.

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DO - 10.1161/01.STR.32.6.1341

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C2 - 11387497

AN - SCOPUS:0034992131

VL - 32

SP - 1341

EP - 1348

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 6

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