Dokument: Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration
| Titel: | Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68727 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250220-124345-6 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Polzin, Amin [Autor] Benkhoff, Marcel [Autor] Thienel, Manuela [Autor] Barcik, Maike [Autor] Mourikis, Philipp [Autor] Shchurovska, Khrystyna [Autor] Helten, Carolin [Autor] Ehreiser, Vincent [Autor] Zhe, Zhang [Autor] Wulffen, Franziska von [Autor] | |||||||
| Dateien: |
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| Stichwörter: | factor Xa, thromboinflammation, myocardial infarction, platelets | |||||||
| Beschreibung: | Background
Immediate activated factor (F)X (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases. Objectives Therefore, we analyzed platelet-derived effects of long-term FXa inhibition in the setting of acute myocardial infarction (AMI) and stroke. Methods We evaluated the effect of acute versus chronic FXa inhibition on thromboinflammation following AMI and stroke in mice in vivo. Mechanistically, we identified changes in platelet gene expression and proteome under chronic FXa nonvitamin K antagonist oral anticoagulant treatment and characterized its functional consequence on platelet physiology. In a prospectively recruited cohort of patients with AMI, we determined cardiovascular magnetic resonance based cardiac endpoints under FXa nonvitamin K antagonist oral anticoagulant effects on clinical endpoints in a cohort of patients with AMI. Results Chronic but not acute FXa inhibition reduced cerebral and myocardial infarct size and improved cardiac function 24 hours after AMI in mice. Mechanistically, we identified an attenuated thromboinflammatory response with reduced neutrophil extracellular trap formation in mice and patient samples. Proteome and RNA expression analysis of FXa inhibitor treated patients revealed a reduction of key regulators within the membrane trafficking and secretion machinery hampering platelet α and dense granule release. Subsequent, thromboinflammatory neutrophil extracellular trap density in thrombi isolated from stroke and myocardial infarction patients was reduced. Patients with AMI treated with FXa inhibitors showed decreased infarct size after myocardial infarction compared to patients without anticoagulation treatment. Conclusion Long-term FXa inhibition induces antithromboinflammatory proteome signatures in platelets, improving infarct size after myocardial infarction and stroke. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Polzin, A., Benkhoff, M., Thienel, M., Barcik, M., Mourikis, P., Shchurovska, K., Helten, C., Ehreiser, V., Zhe, Z., von Wulffen, F., Theiss, A., Peri, S., Cremer, S., Ahlbrecht, S., Zako, S., Wildeis, L., Al-Kassis, G., Metzen, D., Utz, A., … Petzold, T. (2024). Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration. Journal of Thrombosis and Haemostasis, 23(2), 668–683. https://doi.org/10.1016/j.jtha.2024.10.025 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 20.02.2025 | |||||||
| Dateien geändert am: | 20.02.2025 |
