Platelet Serotonin Aggravates Myocardial Ischemia/Reperfusion Injury via Neutrophil Degranulation
| Autor: | Christoph Koentges, Tim Lämmermann, Korbinian Kienle, Claudia Schoenichen, Daniel Duerschmied, Ludwig Dorner, Benoît Ho-Tin-Noé, Carmen Härdtner, Daniela Stallmann, Claus Normann, Ingo Ahrens, Véronique Ollivier, Paul Walther, Klaus Ley, Maximilian Mauler, Heiko Bugger, Maximilian Schell, Christopher Wippel, Ingo Hilgendorf, Christoph Bode, Dennis Wolf, Thilo Witsch, Timoteo Marchini, Nadine Herr |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Inflammation
030204 cardiovascular system & hematology Pharmacology Article 03 medical and health sciences 0302 clinical medicine INFLAMMATION Physiology (medical) purl.org/becyt/ford/3.2 [https] medicine Platelet REACTIVE OXYGEN SPECIES REPERFUSION INJURY Thrombus NEUTROPHILS 030304 developmental biology 0303 health sciences business.industry SEROTONIN Degranulation medicine.disease INTEGRINS Hemostasis Neutrophil degranulation purl.org/becyt/ford/3 [https] Serotonin medicine.symptom Cardiology and Cardiovascular Medicine business Reperfusion injury BLOOD PLATELETS |
| Zdroj: | Circulation CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | Background: Platelets store large amounts of serotonin that they release during thrombus formation or acute inflammation. This facilitates hemostasis and modulates the inflammatory response. Methods: Infarct size, heart function, and inflammatory cell composition were analyzed in mouse models of myocardial reperfusion injury with genetic and pharmacological depletion of platelet serotonin. These studies were complemented by in vitro serotonin stimulation assays of platelets and leukocytes in mice and men, and by measuring plasma serotonin levels and leukocyte activation in patients with acute coronary syndrome. Results: Platelet-derived serotonin induced neutrophil degranulation with release of myeloperoxidase and hydrogen peroxide (H2O2) and increased expression of membrane-bound leukocyte adhesion molecule CD11b, leading to enhanced inflammation in the infarct area and reduced myocardial salvage. In patients hospitalized with acute coronary syndrome, plasmatic serotonin levels correlated with CD11b expression on neutrophils and myeloperoxidase plasma levels. Long-term serotonin reuptake inhibition - reported to protect patients with depression from cardiovascular events - resulted in the depletion of platelet serotonin stores in mice. These mice displayed a reduction in neutrophil degranulation and preserved cardiac function. In line, patients with depression using serotonin reuptake inhibition, presented with suppressed levels of CD11b surface expression on neutrophils and lower myeloperoxidase levels in blood. Conclusions: Taken together, we identify serotonin as a potent therapeutic target in neutrophil-dependent thromboinflammation during myocardial reperfusion injury. Fil: Mauler, Maximilian. No especifíca; Fil: Herr, Nadine. No especifíca; Fil: Schoenichen, Claudia. No especifíca; Fil: Witsch, Thilo. No especifíca; Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Härdtner, Carmen. No especifíca; Fil: Koentges, Christoph. No especifíca; Fil: Kienle, Korbinian. Max Planck Institute Of Immunobiology And Epigenetics; Alemania Fil: Ollivier, Véronique. Inserm; Francia Fil: Schell, Maximilian. No especifíca; Fil: Dorner, Ludwig. No especifíca; Fil: Wippel, Christopher. No especifíca; Fil: Stallmann, Daniela. No especifíca; Fil: Normann, Claus. No especifíca; Fil: Bugger, Heiko. No especifíca; Fil: Walther, Paul. Universitat Ulm; Alemania Fil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados Unidos Fil: Ahrens, Ingo. No especifíca; Fil: Lämmermann, Tim. Max Planck Institute Of Immunobiology And Epigenetics; Alemania Fil: Ho-Tin-Noé, Benoît. Inserm; Francia Fil: Ley, Klaus. La Jolla Institute for Allergy and Immunology; Estados Unidos Fil: Bode, Christoph. No especifíca; Fil: Hilgendorf, Ingo. No especifíca; Fil: Duerschmied, Daniel. No especifíca |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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