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000179481 0247_ $$2doi$$a10.1038/s41467-022-29341-1
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000179481 1001_ $$00000-0001-5469-3648$$aRohlfing, Anne-Katrin$$b0
000179481 245__ $$aACKR3 regulates platelet activation and ischemia-reperfusion tissue injury.
000179481 260__ $$a[London]$$bNature Publishing Group UK$$c2022
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000179481 520__ $$aPlatelet 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.
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000179481 650_2 $$2MeSH$$aAnimals
000179481 650_2 $$2MeSH$$aBlood Platelets: metabolism
000179481 650_2 $$2MeSH$$aHumans
000179481 650_2 $$2MeSH$$aMice
000179481 650_2 $$2MeSH$$aPlatelet Activation
000179481 650_2 $$2MeSH$$aReperfusion
000179481 650_2 $$2MeSH$$aReperfusion Injury: genetics
000179481 650_2 $$2MeSH$$aReperfusion Injury: metabolism
000179481 650_2 $$2MeSH$$aThrombosis: metabolism
000179481 7001_ $$00000-0003-4034-744X$$aKolb, Kyra$$b1
000179481 7001_ $$aSigle, Manuel$$b2
000179481 7001_ $$aZiegler, Melanie$$b3
000179481 7001_ $$aBild, Alexander$$b4
000179481 7001_ $$aMünzer, Patrick$$b5
000179481 7001_ $$aSudmann, Jessica$$b6
000179481 7001_ $$aDicenta, Valerie$$b7
000179481 7001_ $$aHarm, Tobias$$b8
000179481 7001_ $$00000-0001-9197-4940$$aManke, Mailin-Christin$$b9
000179481 7001_ $$aGeue, Sascha$$b10
000179481 7001_ $$00000-0002-1174-3438$$aKremser, Marcel$$b11
000179481 7001_ $$00000-0002-3428-4107$$aChatterjee, Madhumita$$b12
000179481 7001_ $$00000-0002-0305-2522$$aLiang, Chunguang$$b13
000179481 7001_ $$00000-0003-0759-2056$$avon Eysmondt, Hendrik$$b14
000179481 7001_ $$00000-0003-1886-7625$$aDandekar, Thomas$$b15
000179481 7001_ $$aHeinzmann, David$$b16
000179481 7001_ $$0P:(DE-He78)b676990c2f64e3295740d42e356fb053$$aGünter, Manina$$b17$$udkfz
000179481 7001_ $$avon Ungern-Sternberg, Saskia$$b18
000179481 7001_ $$aBüttcher, Manuela$$b19
000179481 7001_ $$aCastor, Tatsiana$$b20
000179481 7001_ $$aMencl, Stine$$b21
000179481 7001_ $$aLanghauser, Friederike$$b22
000179481 7001_ $$0P:(DE-He78)47a1ded1dddd8c84bd3a6e3f6e1e8769$$aSies, Katharina$$b23$$udkfz
000179481 7001_ $$aAshour, Diyaa$$b24
000179481 7001_ $$aBeker, Mustafa Caglar$$b25
000179481 7001_ $$00000-0002-1318-0974$$aLämmerhofer, Michael$$b26
000179481 7001_ $$0P:(DE-He78)d3dbba28fe1239effd15962787cbc363$$aAutenrieth, Stella E$$b27$$udkfz
000179481 7001_ $$00000-0001-5643-8384$$aSchäffer, Tilman E$$b28
000179481 7001_ $$00000-0001-6952-1486$$aLaufer, Stefan$$b29
000179481 7001_ $$aSzklanna, Paulina$$b30
000179481 7001_ $$aMaguire, Patricia$$b31
000179481 7001_ $$00000-0002-3135-2274$$aHeikenwalder, Matthias$$b32
000179481 7001_ $$aMüller, Karin Anne Lydia$$b33
000179481 7001_ $$aHermann, Dirk M$$b34
000179481 7001_ $$aKilic, Ertugrul$$b35
000179481 7001_ $$00000-0002-9458-5526$$aStumm, Ralf$$b36
000179481 7001_ $$aRamos, Gustavo$$b37
000179481 7001_ $$aKleinschnitz, Christoph$$b38
000179481 7001_ $$aBorst, Oliver$$b39
000179481 7001_ $$00000-0003-2224-0518$$aLanger, Harald F$$b40
000179481 7001_ $$aRath, Dominik$$b41
000179481 7001_ $$00000-0003-1124-9592$$aGawaz, Meinrad$$b42
000179481 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-022-29341-1$$gVol. 13, no. 1, p. 1823$$n1$$p1823$$tNature Communications$$v13$$x2041-1723$$y2022
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