Neutrophil stunning by metoprolol reduces infarct size

被引：166

作者：

Garcia-Prieto, Jaime ^{[1
,2
]}

Villena-Gutierrez, Rocio ^{[1
]}

Gomez, Monica ^{[1
]}

Bernardo, Esther ^{[3
]}

Pun-Garcia, Andres ^{[1
]}

Garcia-Lunar, Ines ^{[1
,2
,4
,5
]}

Crainiciuc, Georgiana ^{[1
]}

Fernandez-Jimenez, Rodrigo ^{[1
,2
,3
]}

Sreeramkumar, Vinatha ^{[1
,4
]}

Bourio-Martinez, Rafael ^{[1
,6
]}

Garcia-Ruiz, Jose M. ^{[1
,2
,7
]}

Serrano del Valle, Alfonso ^{[1
]}

Sanz-Rosa, David ^{[1
,2
,4
]}

Pizarro, Gonzalo ^{[1
,2
,4
,8
]}

Fernandez-Ortiz, Antonio ^{[1
,2
,3
]}

Hidalgo, Andres ^{[1
,9
]}

Fuster, Valentin ^{[1
,10
]}

Ibanez, Borja ^{[1
,2
,11
]}

机构：

[1] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Madrid 28029, Spain

[2] CIBER Enfermedades CardioVasc CIBERCV, Madrid 28029, Spain

[3] Hosp Clin San Carlos, Madrid 28040, Spain

[4] Univ Europea, Sch Biomed Sci, Clin Dept, Madrid 28670, Spain

[5] Hosp Univ Quiron, Madrid 28223, Spain

[6] Hosp Basurto, Bilbao 48013, Spain

[7] HUCA, Oviedo, Spain

[8] Complejo Hosp Ruber Juan Bravo UEM, Madrid 28006, Spain

[9] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, D-80336 Munich, Germany

[10] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA

[11] Fdn Jimenez Diaz, IIS, Dept Cardiol, E-28040 Madrid, Spain

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; ADRENERGIC MODULATION; PLATELET ACTIVATION; BETA-BLOCKERS; UP-REGULATION; IMMUNE CELLS; RECEPTOR; ISCHEMIA; INHIBITION;

D O I：

10.1038/ncomms14780

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 55 条

[1] Block the Ischemia and Reperfusion Damage An Old Adjunctive Drug for a New Reperfusion Strategy [J].

Antoniucci, David .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 63 (22) :2363-2364

[2]

Armstrong PW, 2007, JAMA-J AM MED ASSOC, V297, P43

[3] Association between white blood cell count, epicardial blood flow, myocardial perfusion, and clinical outcomes in the setting of acute myocardial infarction - A Thrombolysis in Myocardial Infarction 10 substudy [J].

Barron, HV ;

Cannon, CP ;

Murphy, SA ;

Braunwald, E ;

Gibson, CM .

CIRCULATION, 2000, 102 (19) :2329-2334

[4] An increased platelet-leukocytes interaction at the culprit site of coronary artery occlusion in acute myocardial infarction: A pathogenic role for "no-reflow" phenomenon? [J].

Botto, Nicoletta ;

Sbrana, Silverio ;

Trianni, Giuseppe ;

Andreassi, Maria Grazia ;

Ravani, Marcello ;

Rizza, Antonio ;

Al-Jabri, Anees ;

Palmieri, Cataldo ;

Berti, Sergio .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2007, 117 (01) :123-130

[5] Rhythmic Modulation of the Hematopoietic Niche through Neutrophil Clearance [J].

Casanova-Acebes, Maria ;

Pitaval, Christophe ;

Weiss, Linnea A. ;

Nombela-Arrieta, Cesar ;

Chevre, Raphael ;

A-Gonzalez, Noelia ;

Kunisaki, Yuya ;

Zhang, Dachuan ;

van Rooijen, Nico ;

Silberstein, Leslie E. ;

Weber, Christian ;

Nagasawa, Takashi ;

Frenette, Paul S. ;

Castrillo, Antonio ;

Hidalgo, Andres .

CELL, 2013, 153 (05) :1025-1035

[6] Effects of nebivolol on platelet activation in hypertensive patients: A comparative study with metoprolol [J].

Celik, Turgay ;

Yuksel, U. Cagdas ;

Iyisoy, Atila ;

Kursaklioglu, Hurkan ;

Ozcan, Omer ;

Kilic, Selim ;

Ozmen, Namik ;

Isik, Ersoy .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2007, 116 (02) :206-211

[7] Cocaine and catecholamines enhance inflammatory cell retention in the coronary circulation of mice by upregulation of adhesion molecules [J].

Chen, Y ;

Ke, QG ;

Xiao, YF ;

Wu, GF ;

Kaplan, E ;

Hampton, TG ;

Malek, S ;

Min, JY ;

Amende, I ;

Morgan, JP .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 288 (05) :H2323-H2331

[8]

Chen Y, 2012, METHODS MOL BIOL, V844, P115, DOI 10.1007/978-1-61779-527-5_8

[9] Stress-induced redistribution of immune cells-From barracks to boulevards to battlefields: A tale of three hormones - Curt Richter Award Winner [J].

Dhabhar, Firdaus S. ;

Malarkey, William B. ;

Neri, Eric ;

McEwen, Bruce S. .

PSYCHONEUROENDOCRINOLOGY, 2012, 37 (09) :1345-1368

[10] Modulation of neutrophil migration and superoxide anion release by metoprolol [J].

Dunzendorfer, S ;

Wiedermann, CJ .

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2000, 32 (06) :915-924

← 1 2 3 4 5 6 →