Format

Send to

Choose Destination
Nat Commun. 2017 Apr 18;8:14780. doi: 10.1038/ncomms14780.

Neutrophil stunning by metoprolol reduces infarct size.

Author information

1
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
2
CIBER de enfermedades CardioVasculares (CIBERCV), 28029 Madrid, Spain.
3
Hospital Clínico San Carlos, 28040 Madrid, Spain.
4
Clinical Department, School of Biomedical Sciences, Universidad Europea, 28670 Madrid, Spain.
5
Hospital Universitario Quirón, 28223 Madrid, Spain.
6
Hospital de Basurto, 48013 Bilbao, Spain.
7
Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain.
8
Complejo Hospitalario Ruber Juan Bravo-UEM, 28006 Madrid, Spain.
9
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, 80336 Munich, Germany.
10
Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of medicine at Mount Sinai, New York, New York 10029, USA.
11
Department of Cardiology, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, 28040 Madrid, Spain.

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.

PMID:
28416795
PMCID:
PMC5399300
DOI:
10.1038/ncomms14780
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center