Neutrophil stunning by metoprolol reduces infarct size

Jaime García-Prieto, Rocío Villena-Gutiérrez, Mónica Gómez, Esther Bernardo, Andrés Pun-García, Inés García-Lunar, Georgiana Crainiciuc, Rodrigo Fernández-Jiménez, Vinatha Sreeramkumar, Rafael Bourio-Martínez, José M García-Ruiz, Alfonso Serrano del Valle, David Sanz-Rosa, Gonzalo Pizarro, Antonio Fernández-Ortiz, Andrés Hidalgo, Valentín Fuster and Borja Ibanez ()
Additional contact information
Jaime García-Prieto: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Rocío Villena-Gutiérrez: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Mónica Gómez: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Esther Bernardo: Hospital Clínico San Carlos
Andrés Pun-García: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Inés García-Lunar: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Georgiana Crainiciuc: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Rodrigo Fernández-Jiménez: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Vinatha Sreeramkumar: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Rafael Bourio-Martínez: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
José M García-Ruiz: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Alfonso Serrano del Valle: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
David Sanz-Rosa: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Gonzalo Pizarro: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Antonio Fernández-Ortiz: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Andrés Hidalgo: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Valentín Fuster: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Borja Ibanez: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract The β1-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.

Date: 2017
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DOI: 10.1038/ncomms14780

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