2026-06-14T05:07:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51232024-09-27T09:32:08Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Garcia-Prieto, Jaime
author
Villena-Gutierrez, Rocio
author
Gomez, Monica
author
Bernardo, Esther
author
Pun-Garcia, Andres
author
Garcia-Lunar, Ines
author
Crainiciuc, Georgiana
author
Fernandez-Jimenez, Rodrigo
author
Sreeramkumar, Vinatha
author
Bourio-Martinez, Rafael
author
Garcia-Ruiz, Jose M
author
Del Valle, Alfonso S.
author
Sanz-Rosa, David
author
Pizarro, Gonzalo
author
Fernandez-Ortiz, Antonio
author
Hidalgo, Andres
author
Fuster, Valentin
author
Ibáñez, Borja
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación Jesús Serra
funder
Fundación Interhospitalaria de Investigación Cardiovascular
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Fundación La Marató TV3
funder
Fundación ProCNIC
2017-10-20T10:23:12Z
2017-10-20T10:23:12Z
2017
Nat Commun. 2017; 8:14780
10.1038/ncomms14780
2041-1723
Nature Communications
28416795
http://hdl.handle.net/20.500.12105/5123
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.
eng
ACUTE MYOCARDIAL-INFARCTION
PERCUTANEOUS CORONARY INTERVENTION
ISCHEMIA-REPERFUSION INJURY
METOCARD-CNIC TRIAL
POLYMORPHONUCLEAR LEUKOCYTES
ADRENERGIC MODULATION
VASCULAR INFLAMMATION
PLATELET ACTIVATION
BETA-BLOCKERS
UP-REGULATION
Neutrophil stunning by metoprolol reduces infarct size
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