Differential regulation of platelet aggregation by matrix metalloproteinases-9 and-2

We have recently found matrix metalloproteinase-2 (MMP-2) in human platelet s and reported that the release of this enzyme during platelet activation s timulates aggregation. We have now identified matrix metalloproteinase-9 (M MP-9) in human platelets and resistance-sized (similar to 200 mu m) arterie s. Resting platelets released small quantities of pro-MMP-9. Maximal releas e of MMP-9 was detected during partial (appr. 30% maximum) aggregation with thrombin, However, maximal release of MMP-2 was associated with maximal ag gregation. MMP-9 antibodies induced aggregation of resting platelets and po tentiated aggregation of platelets induced by thrombin and collagen. Moreov er, MMP-9 microisolated from arteries as well as recombinant human MMP-9 (0 .1-30 ng/ml) inhibited thrombin and collagen-induced aggregation. We conclu de 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.