Intracellular matrix metalloproteinase-2 (MMP-2) regulates human platelet activation via hydrolysis of talin.

Matrix metalloproteinase (MMP) activity is generally associated with normal or pathological extracellular processes such as tissue remodelling in growth and development or in tumor metastasis and angiogenesis. Platelets contain at least three MMPs, 1, 2 and 9 that have been reported to stimulate or inhibit agonist-induced platelet aggregation via extracellular signals. The non-selective Zn+2 chelating MMP inhibitor, 1,10-phenanthroline, and the serine protease inhibitor, AEBSF, were found to inhibit all tested agonist-induced platelet aggregation reactions.

Effect of low and high dose melagatran and other antithrombotic drugs on platelet aggregation.

Background: Thrombin-induced aggregation of human platelets can be completely inhibited by melagatran, the bioactive form of ximelagatran, an oral direct thrombin inhibitor.

Methods: The potential of melagatran to differentially inhibit alpha- and gamma-thrombins was tested with a synthetic thrombin substrate. Washed human platelets were also employed to determine if melagatran differentially inhibited alpha- and gamma-thrombin-induced platelet aggregation at distinct platelet thrombin receptors.