Abstract 15903: Platelet Glycoprotein IIb/IIIa Receptor Controls the Pro-Angiogenic Effect of Platelet Releasate
Background: Platelet releasate is known to have pro-angiogenic effect on endothelial cells, however, the role of platelet surface receptors in the control of platelet releasate and its pro-angiogenic effect is not well known. The aim of the present study is to analyze the role of GPIIb/IIIa receptors on platelet releasate and its pro-angiogenic effect.
Methods: Freshly isolated human platelets were treated either with GPIIb/IIIa inhibitor tirofiban or vehicle and the angiogenic effect of releasate from these platelets was analyzed on cultured rat coronary microvessel endothelial cells. Proliferation, migration and sprouting of endothelial cells was quantified by crystal violet staining, migration assay and spheroid sprouting assay respectively.
Results: Incubation of RCEC with platelet releasate for 48 hrs resulted in 20±7% increase (n=5; p<0.05 for all further parameters) in cell proliferation, 28±5% increase in migration, and 40±6% increase in endothelial cell sprouting compared to control. Tirofiban (25 ng/ml), a GP IIb/IIIa receptor antagonist, pretreatment of platelets resulted in abrogation of all these effects on endothelial cells. Tirofiban alone, when given directly to endothelial cells had no effect on endothelial cell proliferation, migration and sprouting. Similar effects were also observed with the other GP IIb/IIIa inhibitors, eptifibatide and abciximab. Furthermore, platelet supernatant induced an increase in ERK2 phosphorylation in endothelial cells, which was completely blocked by tirofiban treatment of platelets.
Conclusions: Our data suggest that platelet GP IIb/IIIa receptors are involved in proangiogenic effects of platelet releasate and this could be via enhanced activation of ERK2 signaling. These findings exhibit a potential link between GP IIb/IIIa and new blood vessel formation.
- © 2011 by American Heart Association, Inc.