Differential regulation of platelet aggregation by matrix metalloproteinases-9 and -2.
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.
Fernandez-Patron
C
C
Perinatal Research Centre, Department of Obstetrics/Gynaecology, University of Alberta, Edmonton, Canada.
Martinez-Cuesta
M A
MA
Salas
E
E
Sawicki
G
G
Wozniak
M
M
Radomski
M W
MW
Davidge
S T
ST
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
D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9