Molecular mechanisms of thrombogenesis
Barinov, E.F.; Sulaeva, O.N.
Kardiologiia 52(12): 45-56
2012
ISSN/ISBN: 0022-9040 PMID: 23237441 Document Number: 657792
Platelets are the key elements of hemostasis and optimal model for analysis of normal and altered mechanisms of thrombogenesis. Adhesion of platelets is initiated by von Willebrand factor, collagen, fibronectin, thrombospondin and laminin through GP VI, GPIb-V-IX complex, integrine receptors α(2)β(1), α(IIb)β, and Fc(γ)-receptors IIA. Their activation is accompanied with signalosome formation, increase of intracellular Ca2+ level, proteins phosphorylation, adhesion and degranulation of platelets. Major stimulators of progression phase are humoral factors and factors accumulated in dense granules of platelets, which include ADP, TA2, epinephrine, serotonin and thrombin. Their action is mediated by stimulation of G-protein coupled receptors: Gq, Gi, Gs, Gz, G12, G13, which can modulate activity of adenilate cyclase, phospholipase C, phosphoinositid-3-kinase, p115-RhoGEF and promote recruitment of platelets in the zone of injury. The phase of stabilization is due to contact-dependent signaling by integrins - predominantly α(IIb)β(3), which ligand is fibrinogen, inducing reorganization of cytoskeleton in platelets, formation of strong intercellular junctions and retraction of thrombus.