Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/5123
Título
Neutrophil stunning by metoprolol reduces infarct size
Autor(es)
Garcia-Prieto, Jaime CNIC | Villena-Gutierrez, Rocio CNIC | Gomez, Monica CNIC | Bernardo, Esther | Pun-Garcia, Andres CNIC | Garcia-Lunar, Ines CNIC | Crainiciuc, Georgiana CNIC | Fernandez-Jimenez, Rodrigo CNIC | Sreeramkumar, Vinatha CNIC | Bourio-Martinez, Rafael CNIC | Garcia-Ruiz, Jose M CNIC | Del Valle, Alfonso S. CNIC | Sanz-Rosa, David CNIC | Pizarro, Gonzalo CNIC | Fernandez-Ortiz, Antonio CNIC | Hidalgo, Andres CNIC | Fuster, Valentin CNIC | Ibáñez, Borja CNIC
Fecha de publicación
2017
Cita
Nat Commun. 2017; 8:14780
Idioma
Inglés
Tipo de documento
journal article
Resumen
The beta 1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation. Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade of PSGL-1, the receptor involved in neutrophil-platelet interactions, fully abrogated metoprolol's infarct-limiting effects. The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients. Metoprolol inhibits neutrophil-platelet interactions in AMI patients by targeting neutrophils. Identification of the relevant role of ADRB1 in haematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies.
Palabras clave
ACUTE MYOCARDIAL-INFARCTION | PERCUTANEOUS CORONARY INTERVENTION | ISCHEMIA-REPERFUSION INJURY | METOCARD-CNIC TRIAL | POLYMORPHONUCLEAR LEUKOCYTES | ADRENERGIC MODULATION | VASCULAR INFLAMMATION | PLATELET ACTIVATION | BETA-BLOCKERS | UP-REGULATION
Versión en línea
DOI
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![Acceso Abierto Acceso Abierto](/themes/Mirage2/images/openAccess.png)
- Nombre:
- NeutrophilStunningByMetoprolol ...
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- Formato:
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![Acceso Abierto Acceso Abierto](/themes/Mirage2/images/openAccess.png)
- Nombre:
- NeutrophilStunningByMetoprolol ...
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- 24.36Mb
- Formato:
- Video QuickTime