Differential Regulation of Platelet Aggregation by Matrix Metalloproteinases-9 and -2

Carlos Fernandez-Patron; Maria A. Martinez-Cuesta; Eduardo Salas; Grzegorz Sawicki; Mieczyslaw Wozniak; Marek W. Radomski; Sandra T. Davidge

doi:10.1055/s-0037-1614906

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(06): 1730-1735
DOI: 10.1055/s-0037-1614906

Rapid Communication

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Differential Regulation of Platelet Aggregation by Matrix Metalloproteinases-9 and -2

Carlos Fernandez-Patron

¹From the Perinatal Research Centre, 232 HMRC, Departments of Obstetrics/Gynaecology and Physiology, University of Alberta, Edmonton, Alberta, Canada

,

Maria A. Martinez-Cuesta

²Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada

³Division of Research and Development Lácer, SA, Sardenya, Barcelona, Spain

,

Eduardo Salas

²Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada

³Division of Research and Development Lácer, SA, Sardenya, Barcelona, Spain

,

Grzegorz Sawicki

²Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada

,

Mieczyslaw Wozniak

⁴Department of Clinical Chemistry, Medical University, Wroclaw, Poland

,

Marek W. Radomski

²Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada

,

Sandra T. Davidge

¹From the Perinatal Research Centre, 232 HMRC, Departments of Obstetrics/Gynaecology and Physiology, University of Alberta, Edmonton, Alberta, Canada

› Author Affiliations

Abstract

Summary

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 (~200 μm) 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.

Keywords

MMPs - vascular - platelets - aggregation

Full Text

References

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