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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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983782/ https://www.ncbi.nlm.nih.gov/pubmed/35383158 http://dx.doi.org/10.1038/s41467-022-29341-1 |
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| author | Rohlfing, Anne-Katrin Kolb, Kyra Sigle, Manuel Ziegler, Melanie Bild, Alexander Münzer, Patrick Sudmann, Jessica Dicenta, Valerie Harm, Tobias Manke, Mailin-Christin Geue, Sascha Kremser, Marcel Chatterjee, Madhumita Liang, Chunguang von Eysmondt, Hendrik Dandekar, Thomas Heinzmann, David Günter, Manina von Ungern-Sternberg, Saskia Büttcher, Manuela Castor, Tatsiana Mencl, Stine Langhauser, Friederike Sies, Katharina Ashour, Diyaa Beker, Mustafa Caglar Lämmerhofer, Michael Autenrieth, Stella E. Schäffer, Tilman E. Laufer, Stefan Szklanna, Paulina Maguire, Patricia Heikenwalder, Matthias Müller, Karin Anne Lydia Hermann, Dirk M. Kilic, Ertugrul Stumm, Ralf Ramos, Gustavo Kleinschnitz, Christoph Borst, Oliver Langer, Harald F. Rath, Dominik Gawaz, Meinrad |
| author_facet | Rohlfing, Anne-Katrin Kolb, Kyra Sigle, Manuel Ziegler, Melanie Bild, Alexander Münzer, Patrick Sudmann, Jessica Dicenta, Valerie Harm, Tobias Manke, Mailin-Christin Geue, Sascha Kremser, Marcel Chatterjee, Madhumita Liang, Chunguang von Eysmondt, Hendrik Dandekar, Thomas Heinzmann, David Günter, Manina von Ungern-Sternberg, Saskia Büttcher, Manuela Castor, Tatsiana Mencl, Stine Langhauser, Friederike Sies, Katharina Ashour, Diyaa Beker, Mustafa Caglar Lämmerhofer, Michael Autenrieth, Stella E. Schäffer, Tilman E. Laufer, Stefan Szklanna, Paulina Maguire, Patricia Heikenwalder, Matthias Müller, Karin Anne Lydia Hermann, Dirk M. Kilic, Ertugrul Stumm, Ralf Ramos, Gustavo Kleinschnitz, Christoph Borst, Oliver Langer, Harald F. Rath, Dominik Gawaz, Meinrad |
| author_sort | Rohlfing, Anne-Katrin |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8983782 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-89837822022-04-22 ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury Rohlfing, Anne-Katrin Kolb, Kyra Sigle, Manuel Ziegler, Melanie Bild, Alexander Münzer, Patrick Sudmann, Jessica Dicenta, Valerie Harm, Tobias Manke, Mailin-Christin Geue, Sascha Kremser, Marcel Chatterjee, Madhumita Liang, Chunguang von Eysmondt, Hendrik Dandekar, Thomas Heinzmann, David Günter, Manina von Ungern-Sternberg, Saskia Büttcher, Manuela Castor, Tatsiana Mencl, Stine Langhauser, Friederike Sies, Katharina Ashour, Diyaa Beker, Mustafa Caglar Lämmerhofer, Michael Autenrieth, Stella E. Schäffer, Tilman E. Laufer, Stefan Szklanna, Paulina Maguire, Patricia Heikenwalder, Matthias Müller, Karin Anne Lydia Hermann, Dirk M. Kilic, Ertugrul Stumm, Ralf Ramos, Gustavo Kleinschnitz, Christoph Borst, Oliver Langer, Harald F. Rath, Dominik Gawaz, Meinrad Nat Commun Article 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. Nature Publishing Group UK 2022-04-05 /pmc/articles/PMC8983782/ /pubmed/35383158 http://dx.doi.org/10.1038/s41467-022-29341-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Rohlfing, Anne-Katrin Kolb, Kyra Sigle, Manuel Ziegler, Melanie Bild, Alexander Münzer, Patrick Sudmann, Jessica Dicenta, Valerie Harm, Tobias Manke, Mailin-Christin Geue, Sascha Kremser, Marcel Chatterjee, Madhumita Liang, Chunguang von Eysmondt, Hendrik Dandekar, Thomas Heinzmann, David Günter, Manina von Ungern-Sternberg, Saskia Büttcher, Manuela Castor, Tatsiana Mencl, Stine Langhauser, Friederike Sies, Katharina Ashour, Diyaa Beker, Mustafa Caglar Lämmerhofer, Michael Autenrieth, Stella E. Schäffer, Tilman E. Laufer, Stefan Szklanna, Paulina Maguire, Patricia Heikenwalder, Matthias Müller, Karin Anne Lydia Hermann, Dirk M. Kilic, Ertugrul Stumm, Ralf Ramos, Gustavo Kleinschnitz, Christoph Borst, Oliver Langer, Harald F. Rath, Dominik Gawaz, Meinrad ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury |
| title | ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury |
| title_full | ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury |
| title_fullStr | ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury |
| title_full_unstemmed | ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury |
| title_short | ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury |
| title_sort | ackr3 regulates platelet activation and ischemia-reperfusion tissue injury |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983782/ https://www.ncbi.nlm.nih.gov/pubmed/35383158 http://dx.doi.org/10.1038/s41467-022-29341-1 |
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