biostudies-literatureRohlfing AKDeutsche Forschungsgemeinschaft1823https://www.ebi.ac.uk/biostudies/studies/S-EPMC8983782biostudies-literatureUnknown13(1)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 agoNature communicationsACKR3 regulates platelet activation and ischemia-reperfusion tissue injury.PMC8983782374031971190538538Schaffer TEDicenta VRohlfing AKChatterjee MMencl SMaguire PCastor TSzklanna PLaufer SHeikenwalder MLiang CZiegler MHeinzmann DKremser MLanger HFDandekar TSies KBild AButtcher MManke MCGunter MStumm RRath Dvon Eysmondt HHarm TLanghauser FMuller KALSigle MLammerhofer MAutenrieth SEKilic EKolb KGeue SRamos GSudmann JKleinschnitz CBorst OGawaz Mvon Ungern-Sternberg SHermann DMBeker MCMunzer PAshour DfalseACKR3 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 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 ago2022-01-01T00:00:00Z2022 Apr2025-04-22T19:02:59.556Z2025-04-06T02:40:28.206ZS-EPMC89837823538315810.1038/s41467-022-29341-1