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美托洛尔使中性粒细胞“失活”，减少梗死面积。

Neutrophil stunning by metoprolol reduces infarct size.

机构信息

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.

CIBER de enfermedades CardioVasculares (CIBERCV), 28029 Madrid, Spain.

出版信息

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

DOI:10.1038/ncomms14780
PMID:28416795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5399300/
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.

摘要

β1 肾上腺素能受体（ADRB1）拮抗剂美托洛尔可减少急性心肌梗死（AMI）患者的梗死面积。普遍的观点是，美托洛尔主要作用于心肌细胞。在这里，我们证明美托洛尔通过靶向造血细胞来减少再灌注损伤。美托洛尔以 ADRB1 依赖的方式抑制中性粒细胞迁移。美托洛尔通过损害循环血小板有效参与所需的结构和功能重排来作用于中性粒细胞募集的早期阶段，导致血管内动力学不稳定和炎症减弱。中性粒细胞耗竭、造血细胞中 Adrb1 消融或阻断参与中性粒细胞-血小板相互作用的 PSGL-1 受体，完全消除了美托洛尔的梗死限制作用。在接受美托洛尔治疗的 AMI 患者中，中性粒细胞计数与微血管阻塞之间的关联被消除。美托洛尔通过靶向中性粒细胞抑制 AMI 患者中性粒细胞-血小板相互作用。鉴定急性损伤过程中造血细胞中 ADRB1 的相关作用及其调节后的保护作用，为开发新的治疗策略提供了可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14c5/5399300/69273e026309/ncomms14780-f7.jpg
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