The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo
Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl<sub>3</sub>-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 mi...
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MDPI AG
2021-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/22/5349 |
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| author | Lydie Crescence Markus Kramberg Martine Baumann Markus Rey Sebastien Roux Laurence Panicot-Dubois Christophe Dubois Markus A. Riederer |
| author_facet | Lydie Crescence Markus Kramberg Martine Baumann Markus Rey Sebastien Roux Laurence Panicot-Dubois Christophe Dubois Markus A. Riederer |
| author_sort | Lydie Crescence |
| collection | DOAJ |
| description | Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl<sub>3</sub>-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. |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T05:23:19Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-0e5782d9d234401d99bb89284b6efdf42023-11-22T23:50:05ZengMDPI AGJournal of Clinical Medicine2077-03832021-11-011022534910.3390/jcm10225349The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In VivoLydie Crescence0Markus Kramberg1Martine Baumann2Markus Rey3Sebastien Roux4Laurence Panicot-Dubois5Christophe Dubois6Markus A. Riederer7Aix Marseille Université, INSERM 1263, INRAE 1260, C2VN, 27 Boulevard Jean Moulin, 13385 Marseille, FranceDrug Discovery Biology, Idorsia Pharmaceuticals Ltd., CH-4123 Allschwil, SwitzerlandDrug Discovery Biology, Idorsia Pharmaceuticals Ltd., CH-4123 Allschwil, SwitzerlandDrug Discovery Biology, Idorsia Pharmaceuticals Ltd., CH-4123 Allschwil, SwitzerlandDrug Discovery Biology, Idorsia Pharmaceuticals Ltd., CH-4123 Allschwil, SwitzerlandAix Marseille Université, INSERM 1263, INRAE 1260, C2VN, 27 Boulevard Jean Moulin, 13385 Marseille, FranceAix Marseille Université, INSERM 1263, INRAE 1260, C2VN, 27 Boulevard Jean Moulin, 13385 Marseille, FranceDrug Discovery Biology, Idorsia Pharmaceuticals Ltd., CH-4123 Allschwil, SwitzerlandSelatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl<sub>3</sub>-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.https://www.mdpi.com/2077-0383/10/22/5349P2Y12 receptorplateletsthrombosishaemostasisthrombus dissolution |
| spellingShingle | Lydie Crescence Markus Kramberg Martine Baumann Markus Rey Sebastien Roux Laurence Panicot-Dubois Christophe Dubois Markus A. Riederer The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo Journal of Clinical Medicine P2Y12 receptor platelets thrombosis haemostasis thrombus dissolution |
| title | The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo |
| title_full | The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo |
| title_fullStr | The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo |
| title_full_unstemmed | The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo |
| title_short | The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo |
| title_sort | p2y12 receptor antagonist selatogrel dissolves preformed platelet thrombi in vivo |
| topic | P2Y12 receptor platelets thrombosis haemostasis thrombus dissolution |
| url | https://www.mdpi.com/2077-0383/10/22/5349 |
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