Dokument: The bile acid receptor TGR5 inhibits platelet activation and thrombus formation
| Titel: | The bile acid receptor TGR5 inhibits platelet activation and thrombus formation | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68446 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250205-115556-3 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Reusswig, Friedrich [Autor] Reich, Maria [Autor] Wienands, Leonard [Autor] Herebian, Diran [Autor] Keitel-Anselmino, Verena [Autor] Elvers, Margitta [Autor] | |||||||
| Dateien: |
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| Stichwörter: | Bile acid, thrombus formation, TGR5 receptor, platelets | |||||||
| Beschreibung: | Liver failure and cirrhosis are characterized by abnormal hemostasis with aberrant platelet activation. In particular, the consequences of cholestatic liver disease and molecular mechanisms, including the role of bile acids leading to impaired platelet responses, are not well understood. Here, we demonstrate that bile acids inhibit human and murine platelet activation, adhesion and spreading, leading to reduced thrombus formation under flow conditions. We identified the G-protein coupled receptor TGR5 in platelets and provide support for its role as mediator of bile acid-induced impairment of platelet activation. In the liver, TGR5 couples to Gαs proteins, activates the adenylate cyclase to induce a transient cAMP rise and stimulates the MAPK signaling pathway to regulate cholangiocyte proliferation, hepatocyte survival and inflammation. In this report, we demonstrate that the genetic deficiency of TGR5 in mice led to enhanced platelet activation and thrombus formation, suggesting that TGR5 plays an important role in hemostasis. Mechanistically, platelet inhibition is achieved by TGR5 mediated PKA activation and modulation of AKT and ERK1/2 phosphorylation. Thus, this report provides evidence for the ability of TGR5 ligands to reduce platelet activation and identifies TGR5 agonism as a new target for the prevention of cardiovascular diseases. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Reusswig, F., Reich, M., Wienands, L., Herebian, D., Keitel-Anselmino, V., & Elvers, M. (2024). The bile acid receptor TGR5 inhibits platelet activation and thrombus formation. Platelets, 35(1), Article 2322733. https://doi.org/10.1080/09537104.2024.2322733 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 05.02.2025 | |||||||
| Dateien geändert am: | 05.02.2025 |
