ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury.

Autor: Rohlfing AK; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Kolb K; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Sigle M; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Ziegler M; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Bild A; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Münzer P; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Sudmann J; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Dicenta V; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Harm T; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Manke MC; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.; DFG Heisenberg Group Thrombocardiology, University of Tübingen, Tübingen, Germany., Geue S; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Kremser M; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Chatterjee M; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Liang C; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany., von Eysmondt H; Institute of Applied Physics, University of Tübingen, Tübingen, Germany., Dandekar T; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany., Heinzmann D; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Günter M; Department of Dendritic Cells in Infection and Cancer, German Cancer Research Centre, Heidelberg, Germany., von Ungern-Sternberg S; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Büttcher M; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Castor T; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Mencl S; Department of Neurology, University Hospital Essen, Essen, Germany., Langhauser F; Department of Neurology, University Hospital Essen, Essen, Germany., Sies K; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Dermatology, University of Heidelberg, Heidelberg, Germany., Ashour D; Immunocardiology Lab, University Hospital Würzburg, Comprehensive Heart Failure Center (CHFC), Würzburg, Germany., Beker MC; Department of Physiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey., Lämmerhofer M; University of Tübingen, Institute of Pharmaceutical Sciences, Pharmaceutical (Bio-)Analysis, Tübingen, Germany., Autenrieth SE; Department of Dendritic Cells in Infection and Cancer, German Cancer Research Centre, Heidelberg, Germany., Schäffer TE; Institute of Applied Physics, University of Tübingen, Tübingen, Germany., Laufer S; Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, University of Tübingen, Tübingen, Germany., Szklanna P; Conway-SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland., Maguire P; Conway-SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland., Heikenwalder M; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Müller KAL; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Hermann DM; Vascular Neurology, Dementia and Ageing Research, Department of Neurology, Essen, Germany., Kilic E; Department of Physiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey., Stumm R; Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany., Ramos G; Immunocardiology Lab, University Hospital Würzburg, Comprehensive Heart Failure Center (CHFC), Würzburg, Germany., Kleinschnitz C; Department of Neurology, University Hospital Essen, Essen, Germany., Borst O; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.; DFG Heisenberg Group Thrombocardiology, University of Tübingen, Tübingen, Germany., Langer HF; University Hospital, Medical Clinic II, University Heart Center, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Partner Site Hamburg/Lübeck/Kiel, Lübeck, Germany., Rath D; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany., Gawaz M; Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany. meinrad.gawaz@med.uni-tuebingen.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Apr 05; Vol. 13 (1), pp. 1823. Date of Electronic Publication: 2022 Apr 05.
DOI: 10.1038/s41467-022-29341-1
Abstrakt: Platelet activation plays a critical role in thrombosis. Inhibition of platelet activation is a cornerstone in treatment of acute organ ischemia. Platelet ACKR3 surface expression is independently associated with all-cause mortality in CAD patients. In a novel genetic mouse strain, we show that megakaryocyte/platelet-specific deletion of ACKR3 results in enhanced platelet activation and thrombosis in vitro and in vivo. Further, we performed ischemia/reperfusion experiments (transient LAD-ligation and tMCAO) in mice to assess the impact of genetic ACKR3 deficiency in platelets on tissue injury in ischemic myocardium and brain. Loss of platelet ACKR3 enhances tissue injury in ischemic myocardium and brain and aggravates tissue inflammation. Activation of platelet-ACKR3 via specific ACKR3 agonists inhibits platelet activation and thrombus formation and attenuates tissue injury in ischemic myocardium and brain. Here we demonstrate that ACKR3 is a critical regulator of platelet activation, thrombus formation and organ injury following ischemia/reperfusion.
(© 2022. The Author(s).)
Databáze: MEDLINE
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