Platelets release active matrix metalloproteinase-2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirin

Br J Haematol. 2007 Jul;138(2):221-30. doi: 10.1111/j.1365-2141.2007.06632.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aspirin / administration & dosage*
  • Bleeding Time
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Flow Cytometry / methods
  • Hemorrhage / metabolism*
  • Humans
  • Male
  • Matrix Metalloproteinase 14 / blood
  • Matrix Metalloproteinase 2 / blood*
  • Middle Aged
  • Platelet Activation / physiology
  • Platelet Aggregation / physiology
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Count
  • Tissue Inhibitor of Metalloproteinase-2 / blood

Substances

  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14
  • Aspirin