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ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury

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 mega...

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Main Authors: Rohlfing, Anne-Katrin (Author) , Kolb, Kyra (Author) , Sigle, Manuel (Author) , Ziegler, Melanie (Author) , Bild, Alexander (Author) , Münzer, Patrick (Author) , Sudmann, Jessica (Author) , Dicenta, Valerie (Author) , Harm, Tobias (Author) , Manke, Mailin-Christin (Author) , Geue, Sascha (Author) , Kremser, Marcel (Author) , Chatterjee, Madhumita (Author) , Liang, Chunguang (Author) , von Eysmondt, Hendrik (Author) , Dandekar, Thomas (Author) , Heinzmann, David (Author) , Günter, Manina (Author) , von Ungern-Sternberg, Saskia (Author) , Büttcher, Manuela (Author) , Castor, Tatsiana (Author) , Mencl, Stine (Author) , Langhauser, Friederike (Author) , Kommoss, Katharina (Author) , Ashour, Diyaa (Author) , Beker, Mustafa Caglar (Author) , Lämmerhofer, Michael (Author) , Autenrieth, Stella E. (Author) , Schäffer, Tilman (Author) , Laufer, Stefan (Author) , Szklanna, Paulina (Author) , Maguire, Patricia (Author) , Heikenwalder, Matthias (Author) , Müller, Karin Anne Lydia (Author) , Hermann, Dirk M. (Author) , Kilic, Ertugrul (Author) , Stumm, Ralf (Author) , Ramos, Gustavo (Author) , Kleinschnitz, Christoph (Author) , Borst, Oliver (Author) , Langer, Harald F. (Author) , Rath, Dominik (Author) , Gawaz, Meinrad Paul (Author)
Format: Article (Journal)
Language:English
Published: 05 April 2022
In: Nature Communications
Year: 2022, Volume: 13, Pages: 1-20
ISSN:2041-1723
DOI:10.1038/s41467-022-29341-1
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-022-29341-1
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-022-29341-1
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Author Notes:Anne-Katrin Rohlfing, Kyra Kolb, Manuel Sigle, Melanie Ziegler, Alexander Bild, Patrick Münzer, Jessica Sudmann, Valerie Dicenta, Tobias Harm, Mailin-Christin Manke, Sascha Geue, Marcel Kremser, Madhumita Chatterjee, Chunguang Liang, Hendrik von Eysmondt, Thomas Dandekar, David Heinzmann, Manina Günter, Saskia von Ungern-Sternberg, Manuela Büttcher, Tatsiana Castor, Stine Mencl, Friederike Langhauser, Katharina Sies, Diyaa Ashour, Mustafa Caglar Beker, Michael Lämmerhofer, Stella E. Autenrieth, Tilman E. Schäffer, Stefan Laufer, Paulina Szklanna, Patricia Maguire, Matthias Heikenwalder, Karin Anne Lydia Müller, Dirk M. Hermann, Ertugrul Kilic, Ralf Stumm, Gustavo Ramos, Christoph Kleinschnitz, Oliver Borst, Harald F. Langer, Dominik Rath & Meinrad Gawaz
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Summary: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.
Item Description:Gesehen am 18.05.2022
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-022-29341-1

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