title: Differential regulation of platelet aggregation by matrix metalloproteinases-9 and -2.
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.
authors.affiliation: Perinatal Research Centre, Department of Obstetrics/Gynaecology, University of Alberta, Edmonton, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Fernandez-Patron
authors.forename: M A
authors.initials: MA
authors.lastname: Martinez-Cuesta
authors.forename: E
authors.initials: E
authors.lastname: Salas
authors.forename: G
authors.initials: G
authors.lastname: Sawicki
authors.forename: M
authors.initials: M
authors.lastname: Wozniak
authors.forename: M W
authors.initials: MW
authors.lastname: Radomski
authors.forename: S T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D001158:Arteries / Q000166:cytology / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9