Neutrophil stunning by metoprolol reduces infarct size

作者：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; Serrano del Valle Alfonso; Sanz Rosa David; Pizarro Gonzalo; Fernandez Ortiz Antonio; Hidalgo Andres; Fuster Valentin; Ibanez Borja^*

来源：Nature Communications, 2017, 8(1): 14780.

DOI：10.1038/ncomms14780

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.

• 出版日期2017-4-18