RT Journal Article
T1 Escitalopram Impairs Thrombin-Induced Platelet Response, Cytoskeletal Assembly and Activation of Associated Signalling Pathways
A1 López Víchez, Irene
A1 Jerez Dolz, Didac
A1 Díaz Ricart, Maribel
A1 Navarro, Víctor
A1 Urooj Zafar, M
A1 Zamorano León, José Javier
A1 López Farre, Antonio José
A1 Badimon, Juan
A1 Gasto, Cristóbal
A1 Escolar, Ginés
AB Background Serotonin reuptake inhibitors (SSRIs) may impair platelet function. Thrombin is a strong platelet agonist causing irreversible aggregation, release of granules' contents, cytoskeletal rearrangement and activation of signalling pathways. We investigated the effects of the SSRI escitalopram (SCIT) on thrombin-induced platelet response. Methods Isolated platelets were exposed to SCIT and activated with thrombin. We evaluated (1) platelet response by aggregometry and flow cytometry; (2) modifications in cytoskeleton proteins and signalling pathways by electrophoresis and Western blot; and (3) ultrastructural changes in platelets by electron microscopy. Results SCIT inhibited platelet response to thrombin, measured as platelet aggregation and expression of activation markers CD62-P and CD63 from platelet granules. Platelet aggregation decreased in a dose-dependent manner, reaching statistical significance with SCIT ≥32 µg/mL (65.4 ± 6.8% vs. 77.7 ± 2.5% for controls; p < 0.05). Expression of activation markers was statistically reduced with SCIT ≥20 µg/mL (p < 0.05). SCIT impaired the polymerization of the actin cytoskeleton and association of contractile proteins during activation with thrombin (p < 0.05 with SCIT ≥50 µg/mL). Resting platelets incubated with SCIT became most spherical, with increased platelet roundness (p < 0.01, SCIT 50 µg/mL vs. control). SCIT interfered with signalling pathways modulated by thrombin (RhoA, PKC, Erk1/2 and PI3K/AKT). Conclusions Our data indicate that SCIT inhibits thrombin-induced platelet response and interferes with cytoskeletal assembly and related signalling pathways, thus resulting in compromised release of granules' contents, reduced platelet activation and aggregation. These mechanisms may explain the antithrombotic benefits observed in patients treated with this SSRI, and could become new therapeutic targets for future antithrombotic strategies.
PB Thieme Gruppe
SN 0340-6245
YR 2017
FD 2017-07-01
LK https://hdl.handle.net/20.500.14352/99282
UL https://hdl.handle.net/20.500.14352/99282
LA eng
NO Lopez-Vilchez I, Jerez-Dolz D, Diaz-Ricart M, Navarro V, Zafar MU, Zamorano-Leon J, Lopez-Farre A, Badimon JJ, Gasto C, Escolar G. Escitalopram Impairs Thrombin-Induced Platelet Response, Cytoskeletal Assembly and Activation of Associated Signalling Pathways. Thromb Haemost. 2017 Dec;117(12):2312-2321. doi: 10.1160/TH17-04-0288. Epub 2017 Dec 6. PMID: 29212119.
NO Instituto de Salud Carlos III
NO Red de Investigación Cardiovascular
NO European Regional Development Fund
NO Ministerio de Economía y Competitividad
NO Technology Development Projects in Health
NO CIBERSAM
DS Docta Complutense
RD 18 abr 2025