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oai:repisalud.isciii.es:20.500.12105/51232024-09-27T09:32:08Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2017 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. Nat Commun. 2017; 8:14780 10.1038/ncomms14780 2041-1723 Nature Communications 28416795 http://hdl.handle.net/20.500.12105/5123 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