Neutrophil stunning by metoprolol reduces infarct size

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...

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Detalhes bibliográficos
Autores: Garcia-Prieto, Jaime, Villena-Gutierrez, Rocio, Gomez, Monica, Bernardo, Esther, Pun-Garcia, Andres, Garcia-Lunar, Ines, Crainiciuc, Georgiana, Fernandez-Jimenez, Rodrigo, Sreeramkumar, Vinatha, Bourio-Martinez, Rafael, Garcia-Ruiz, Jose M, Del Valle, Alfonso S., Sanz-Rosa, David, Pizarro, Gonzalo, Fernandez-Ortiz, Antonio, Hidalgo, Andres, Fuster, Valentin, Ibáñez, Borja
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/5123
Acesso em linha:http://hdl.handle.net/20.500.12105/5123
Access Level:acceso abierto
Palavra-chave:ACUTE MYOCARDIAL-INFARCTION
PERCUTANEOUS CORONARY INTERVENTION
ISCHEMIA-REPERFUSION INJURY
METOCARD-CNIC TRIAL
POLYMORPHONUCLEAR LEUKOCYTES
ADRENERGIC MODULATION
VASCULAR INFLAMMATION
PLATELET ACTIVATION
BETA-BLOCKERS
UP-REGULATION
Descrição
Resumo: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.

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