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Characterization of plasmin-induced platelet aggregation
A Watabe1, M Ohta, N Matsuyama
1Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan.
Research Communications in Molecular Pathology and Pharmacology
|June 1, 1997
Summary
Tissue-plasminogen activator (t-PA) can cause platelet aggregation by generating plasmin, potentially leading to myocardial infarction reocclusion. This plasmin-induced platelet aggregation is inhibited by specific protease inhibitors and involves calcium and RGDS-dependent pathways.
Area of Science:
- Cardiovascular Research
- Hematology
- Biochemistry
Background:
- Myocardial infarction treatment with tissue-plasminogen activator (t-PA) can be complicated by reocclusion.
- The precise mechanisms underlying t-PA-induced reocclusion require further elucidation.
Purpose of the Study:
- To investigate whether plasmin-induced platelet aggregation is a contributing factor to reocclusion after t-PA treatment.
- To identify the molecular mechanisms and binding sites involved in plasmin-platelet interactions.
Main Methods:
- Platelet aggregation assays under various conditions.
- Inhibition studies using serine protease inhibitors (aprotinin, bdellin) and EACA.
- Analysis of extracellular calcium and RGDS sequence involvement.
- Binding experiments with fluorescently labeled plasmin.
- Flow cytometry using anti-plasmin(ogen) monoclonal antibodies.
Main Results:
- t-PA induced platelet aggregation via plasmin generation under specific conditions.
- Plasmin-induced aggregation was inhibited by aprotinin, bdellin, and EACA.
- Extracellular calcium and RGDS-dependent steps were implicated in the aggregation process.
- Plasmin binds to specific sites on platelets, potentially via its N-terminal region, involving protease catalytic and lysine binding sites.
Conclusions:
- Plasmin-induced platelet aggregation is a potential mechanism for reocclusion after t-PA therapy for myocardial infarction.
- Inhibitors targeting plasmin activity and its binding to platelets may offer therapeutic strategies to prevent reocclusion.