Cardiovascular Research Advance Access first published online on June 18, 2009
This version [Corrected Proof] published online on July 7, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp205
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Serotonin enhances platelet procoagulant properties and their activation induced during platelet tissue factor uptake
1 Servicio de Hemoterapia y Hemostasia, Hospital Clinic, Centro de Diagnostico Biomedico, Instituto de Investigaciones Biomedicas August Pi i Sunyer, Universidad de Barcelona, Villarroel 170, 08036 Barcelona, Spain
2 Department of Laboratory and Clinical Medicine and Pediatrics, University of Minnesota, Minneapolis, MN, USA
* Corresponding author. Tel: +34 93 227 54 00 ext. 2034; fax: +34 93 227 93 69.E-mail address: ilopez1{at}clinic.ub.es
Aims: Circulating tissue factor (TF) has been linked to thrombus propagation. Our group demonstrated that platelets possess mechanisms to capture TF-rich microvesicles (TF-MVs). Serotonin facilitates the development of platelets with increased procoagulant activity. An enhanced platelet serotonin uptake has been identified with increased cardiovascular risk. We have investigated the involvement of serotonergic mechanisms facilitating the interaction of human platelets with TF-MVs. Inhibitory strategies aimed at blocking serotonin and coagulation mechanisms were also studied.
Methods and results: Standard aggregometry, flow cytometry, electron microscopy, and thrombin generation assays were performed. TF-MVs induced platelet aggregation in heparinized platelet-rich plasma (PRP) samples; this aggregation was further accelerated by serotonin. In washed platelets, serotonin enhanced platelet aggregation to TF-MVs with a maximum peak of 55.9 ± 1.8 vs. 48.7 ± 2.1% (P < 0.05). Inhibitory strategies with a selective serotonin re-uptake inhibitor and with lepirudin decreased these aggregations. Ultrastructural analysis revealed that serotonin induced platelet pseudopodia formation, thus facilitating the engulfment of TF-MVs. In general, serotonin significantly enhanced (P < 0.05) thrombin generation and the expression of activation markers and procoagulant activity in platelets measured for TF-MVs alone.
Conclusion: Serotonin enhances the interaction of platelets with TF-MVs, increases platelet activation, and potentiates their overall procoagulant activity. The present results could have significant implications in thrombus formation and in the thrombogenic profile of pathological situations with increased cardiovascular risk.
KEYWORDS Serotonin; Tissue factor; Platelet activation; Procoagulant effect; Thrombogenicity
Time for primary review: 41 days