Platelets release active matrix metalloproteinase-2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirin.
When stimulated in vitro, human platelets release matrix metalloproteinase-2 (MMP-2) that, in turn, potentiates platelet activation. The present study investigated if MMP-2 is released from activated platelets in vivo in humans and whether aspirin inhibits this release. MMP-2 levels were measured by zymography, immunoblotting, flow-cytometry and an activity assay system, in plasma prepared from blood emerging from a skin wound inflicted for the measurement of the bleeding time (shed blood) and simultaneously from venous blood in 27 healthy human volunteers. In a subgroup, the same measurements were carried out before and 1 h after aspirin intake. MMP-2 was significantly higher in shed blood than in venous blood and increased progressively, consistent with ongoing platelet activation. A significant correlation was evident between platelet number and MMP-2 in shed blood; platelet MMP-2 content in shed blood was lower than that of platelets in venous blood. The level of active MMP-2 released by activated platelets in vivo was within the range of concentrations that potentiate platelet activation. Aspirin did not reduce MMP-2 release in vivo. In conclusion, MMP-2 is released from platelets in vivo in humans at a localised site of vessel wall damage in amounts sufficient to potentiate platelet aggregation; aspirin does not reduce this release.
Falcinelli
Emanuela
E
Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy.
Giannini
Silvia
S
Boschetti
Enrico
E
Gresele
Paolo
P
D000284:Administration, Oral; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005434:Flow Cytometry / Q000379:methods; D006470:Hemorrhage / Q000378:metabolism*; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010976:Platelet Count; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14; D001241:Aspirin