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Cited by 216

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Neutrophil stunning by metoprolol reduces infarct size

Open access
García-Prieto, Jaime, Villena-Gutiérrez, Rocío, Gómez, Mónica, Bernardo, Esther, Pun-García, Andrés, García-Lunar, Inés, Crainiciuc, Georgiana, Fernández-Jiménez, Rodrigo, Sreeramkumar, Vinatha, Bourio-Martínez, Rafael, García-Ruiz, José M, del Valle, Alfonso Serrano, Sanz-Rosa, David, Pizarro, Gonzalo, Fernández-Ortiz, Antonio, Hidalgo, Andrés, Fuster, Valentín, Ibanez, Borja·2017·Nature Communications

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.

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Crossref · 10.1038/ncomms14780

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Metadata

Authors
García-Prieto, J., Villena-Gutiérrez, R., Gómez, M., Bernardo, E., Pun-García, A., García-Lunar, I., Crainiciuc, G., Fernández-Jiménez, R., Sreeramkumar, V., Bourio-Martínez, R., García-Ruiz, J. M., del Valle, A. S., Sanz-Rosa, D., Pizarro, G., Fernández-Ortiz, A., Hidalgo, A., Fuster, V., & Ibanez, B.
Venue
Nature Communications
Published
2017-04-18
Volume
8
Issue
1
Pages
14780-14780
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2605618959
Cited by
216
References
4
FWCI
14.83
Type
journal article
Language
en
Open access
gold

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