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Differential regulation of platelet aggregation by matrix metalloproteinases-9 and -2
C Fernandez-Patron1, M A Martinez-Cuesta, E Salas
1Perinatal Research Centre, Department of Obstetrics/Gynaecology, University of Alberta, Edmonton, Canada.
Abstract:
We have recently found matrix metalloproteinase-2 (MMP-2) in human platelets and reported that the release of this enzyme during platelet activation stimulates aggregation. We have now identified matrix metalloproteinase-9 (MMP-9) in human platelets and resistance-sized (approximately 200 microm) arteries. Resting platelets released small quantities of pro-MMP-9. Maximal release of MMP-9 was detected during partial (appr. 30% maximum) aggregation with thrombin. However, maximal release of MMP-2 was associated with maximal aggregation. MMP-9 antibodies induced aggregation of resting platelets and potentiated aggregation of platelets induced by thrombin and collagen. Moreover, MMP-9 microisolated from arteries as well as recombinant human MMP-9 (0.1-30 ng/ml) inhibited thrombin and collagen-induced aggregation. We conclude that MMP-9 is an inhibitor of aggregation and in this action opposes the effects of MMP-2. The MMP-2/MMP-9 system may play an important role in the regulation of platelet-platelet and platelet-vessel wall interactions.
Insights
Matrix metalloproteinase-9 (MMP-9) in human platelets inhibits aggregation, opposing MMP-2
Area of Science:
- Biochemistry
- Hematology
- Vascular Biology
Background:
- Matrix metalloproteinase-2 (MMP-2) is present in human platelets and promotes aggregation.
- The role of other matrix metalloproteinases in platelet function is not fully understood.
Purpose of the Study:
- To identify and characterize matrix metalloproteinase-9 (MMP-9) in human platelets.
- To investigate the role of MMP-9 in platelet aggregation and its interaction with MMP-2.
Main Methods:
- Identification of MMP-9 in human platelets and arteries.
- Measurement of MMP-9 release during platelet activation.
- Assessment of MMP-9's effect on platelet aggregation using antibodies and recombinant protein.
Main Results:
- MMP-9 was identified in human platelets and arteries.
- MMP-9 release was detected during platelet aggregation, with maximal release during partial aggregation.
- MMP-9 inhibited thrombin- and collagen-induced platelet aggregation, opposing MMP-2's pro-aggregatory effects.
Conclusions:
- MMP-9 acts as an inhibitor of platelet aggregation.
- The MMP-2/MMP-9 system plays a crucial role in regulating platelet-platelet and platelet-vessel wall interactions.