Document Detail


The interaction between components of the fibrinolytic system and GPIb/V/IX of platelets thrombus formation in mice.
MedLine Citation:
PMID:  11030738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The interaction of fibrinolytic components with GPIb/V/IX of platelets on thrombus formation, was investigated in mice deficient in tissue type (tPA-/-), urokinase type plasminogen activator (uPA-/-) or plasminogen activator inhibitor-1 (PAI-1-/-) and in their wild type control (tPA+/+, uPA+/+, PAI-1+/+). A thrombus was induced in the murine carotid artery using a photochemical reaction. The times to occlusion after the initiation of endothelial injury in all wild type mice was within 12 min, and no significant changes in occlusion delay were observed in uPA-/- and tPA-/- mice compared to wild type mice, whereas that of PAI-1 mice were significantly prolonged (16.9+/-2.9 min, P<0.05). When high molecular weight aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein Ib/V/IX, was administered, the time to occlusion was prolonged in a dose-dependent manner in all types of mice. However, when this compound was injected in tPA-/- mice, the most significant changes were observed: i.e. the estimated ED(50) was 20.2 times higher than that in tPA+/+ mice, but the estimated ED(50) in uPA-/- mice was not changed as compared with that of wild type mice. On the other hand, when ATA was injected in PAI-1-/- mice, the estimated ED(50) was significantly decreased (P<0.05). Platelet aggregation induced by botrocetin was not significantly different among all types of mice. The bleeding time was prolonged in a dose dependent-manner when ATA was injected in all types of mice. In conclusion, the antithrombotic effect of inhibition of platelet GPIb/V/IX is severely affected by the absence or presence of tPA-production on thrombus formation and the inhibition of PAI-1 could enhance this antithrombotic effect.
Authors:
H Matsuno; O Kozawa; S Ueshima; O Matsuo; D Collen; T Uematsu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  131     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-12-05     Completed Date:  2000-12-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  858-64     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aurintricarboxylic Acid / pharmacology
Bleeding Time
Fibrinolysis*
Fibrinolytic Agents / pharmacology*
Mice
Plasminogen Activator Inhibitor 1 / physiology
Platelet Aggregation / drug effects
Platelet Glycoprotein GPIb-IX Complex / physiology*
Thrombosis / etiology*
Tissue Plasminogen Activator / physiology
Urokinase-Type Plasminogen Activator / physiology
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Plasminogen Activator Inhibitor 1; 0/Platelet Glycoprotein GPIb-IX Complex; 4431-00-9/Aurintricarboxylic Acid; EC 3.4.21.68/Tissue Plasminogen Activator; EC 3.4.21.73/Urokinase-Type Plasminogen Activator
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