Publication: TRAP-induced platelet reactivity is inhibited by omega-3 fatty acid-derived prostaglandin E3 (PGE3)
Authors
Osete Albaladejo, José Miguel ; García Candel, Faustino ; Fernández Gómez, Francisco José ; Blanquer Blanquer, Miguel ; Marín Atucha, Noemí ; García-Estañ López, Joaquín ; Iyú Espinosa, David
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Facultades de la UMU::Facultad de Medicina
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Publisher
MDPI
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DOI
https://doi.org/10.3390/biomedicines12122855
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info:eu-repo/semantics/article
Description
Abstract
Background: Prostaglandins are naturally occurring local mediators that can participate in the modulation of the cardiovascular system through their interaction with Gs/Gi-coupled receptors in different tissues and cells, including platelets. Thrombin is one of the most important factors that regulates platelet reactivity and coagulation. Clinical trials have consistently shown that omega-3 fatty acid supplementation lowers the risk for cardiovascular mortality and morbidity. Since omega-3 fatty acids are the main precursors of PGE3 in vivo, it would be relevant to investigate the effects of PGE3 on Thrombin Receptor Activating Peptide (TRAP-6)-induced platelet reactivity to determine the receptors and possible mechanisms of action of these compounds. Methods: We have measured platelet aggregation, P-selectin expression, and vasodilator-stimulated phosphoprotein (VASP) phosphorylation to evaluate platelet reactivity induced by TRAP-6 to determine the effects of PGE3 on platelet function. Results: We assessed the ability of DG-041, a selective prostanoid EP3 receptor antagonist, and of ONO-AE3-208, a selective prostanoid EP4 receptor antagonist, to modify the effects of PGE3. PGE3 inhibited TRAP-6-induced platelet aggregation and activation. This inhibition was enhanced in the presence of a Gi-coupled EP3 receptor antagonist and abolished in the presence of a Gs-coupled EP4 receptor antagonist. The effects of PGE3 were directly related to changes in cAMP, assessed by VASP phosphorylation. Conclusions: The general effects of PGE3 on human platelet reactivity are the consequence of a balance between activatory and inhibitory effects at receptors that have contrary effects on adenylate cyclase. These results indicate a potential mechanism by which omega-3 fatty acids underlie cardioprotective effects.
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Citation
Osete, J.-M., García-Candel, F., Fernández-Gómez, F.-J., Blanquer, M., Atucha, N. M., García-Estañ, J., & Iyú, D. (2024). TRAP-Induced Platelet Reactivity Is Inhibited by Omega-3 Fatty Acid-Derived Prostaglandin E3 (PGE3). Biomedicines, 12(12), 2855. https://doi.org/10.3390/biomedicines12122855
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