The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo
| Autor: | Martine Baumann, Laurence Panicot-Dubois, Markus Rey, Sébastien Roux, Markus A. Riederer, Lydie Crescence, Christophe Dubois, Markus Kramberg |
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| Přispěvatelé: | Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Idorsia Pharmaceut |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Pharmacology Article Subcutaneous injection P2Y12 In vivo medicine Platelet cardiovascular diseases Thrombus thrombosis business.industry General Medicine medicine.disease Thrombosis medicine.anatomical_structure haemostasis platelets cardiovascular system Medicine P2Y12 receptor thrombus dissolution business Intravital microscopy Blood vessel |
| Zdroj: | Journal of Clinical Medicine Journal of Clinical Medicine, 2021, 10 (22), pp.5349. ⟨10.3390/jcm10225349⟩ Journal of Clinical Medicine, Vol 10, Iss 5349, p 5349 (2021) Volume 10 Issue 22 |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm10225349⟩ |
| Popis: | Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl3-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice. In addition, in a modified Folts thrombosis model in guinea pigs, selatogrel prevented a decrease in blood-flow, indicative of the inhibition of ongoing thrombosis, approximately 10 min after subcutaneous injection. Selatogrel fully normalised blood flow therefore, we speculate that it may not only prevent, but also dissolve, platelet thrombi. Thrombus dissolution was investigated using real-time intravital microscopy in mice. The infusion of selatogrel during ongoing platelet thrombus formation stopped growth and induced the dissolution of the preformed platelet thrombus. In addition, platelet-rich thrombi were given 30 min to consolidate in vivo. The infusion of selatogrel dissolved the preformed and consolidated platelet thrombi. Dissolution was limited to the disintegration of the occluding part of the platelet thrombi, leaving small mural platelet aggregates to seal the blood vessel. Therefore, our experiments uncovered a novel advantage of selatogrel: the dissolution of pre-formed thrombi without the disintegration of haemostatic seals, suggesting a bipartite benefit of the early application of selatogrel in patients with acute thrombosis. |
| Databáze: | OpenAIRE |
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