TY  - JOUR
AU  - Rohlfing, Anne-Katrin
AU  - Kolb, Kyra
AU  - Sigle, Manuel
AU  - Ziegler, Melanie
AU  - Bild, Alexander
AU  - Münzer, Patrick
AU  - Sudmann, Jessica
AU  - Dicenta, Valerie
AU  - Harm, Tobias
AU  - Manke, Mailin-Christin
AU  - Geue, Sascha
AU  - Kremser, Marcel
AU  - Chatterjee, Madhumita
AU  - Liang, Chunguang
AU  - von Eysmondt, Hendrik
AU  - Dandekar, Thomas
AU  - Heinzmann, David
AU  - Günter, Manina
AU  - von Ungern-Sternberg, Saskia
AU  - Büttcher, Manuela
AU  - Castor, Tatsiana
AU  - Mencl, Stine
AU  - Langhauser, Friederike
AU  - Sies, Katharina
AU  - Ashour, Diyaa
AU  - Beker, Mustafa Caglar
AU  - Lämmerhofer, Michael
AU  - Autenrieth, Stella E
AU  - Schäffer, Tilman E
AU  - Laufer, Stefan
AU  - Szklanna, Paulina
AU  - Maguire, Patricia
AU  - Heikenwalder, Matthias
AU  - Müller, Karin Anne Lydia
AU  - Hermann, Dirk M
AU  - Kilic, Ertugrul
AU  - Stumm, Ralf
AU  - Ramos, Gustavo
AU  - Kleinschnitz, Christoph
AU  - Borst, Oliver
AU  - Langer, Harald F
AU  - Rath, Dominik
AU  - Gawaz, Meinrad
TI  - ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury.
JO  - Nature Communications
VL  - 13
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2022-00695
SP  - 1823
PY  - 2022
AB  - 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.
KW  - Animals
KW  - Blood Platelets: metabolism
KW  - Humans
KW  - Mice
KW  - Platelet Activation
KW  - Reperfusion
KW  - Reperfusion Injury: genetics
KW  - Reperfusion Injury: metabolism
KW  - Thrombosis: metabolism
LB  - PUB:(DE-HGF)16
C6  - pmid:35383158
DO  - DOI:10.1038/s41467-022-29341-1
UR  - https://inrepo02.dkfz.de/record/179481
ER  -