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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2021
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oai:doaj.org-article:0e5782d9d234401d99bb89284b6efdf42021-11-25T18:01:58ZThe P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo10.3390/jcm102253492077-0383https://doaj.org/article/0e5782d9d234401d99bb89284b6efdf42021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/22/5349https://doaj.org/toc/2077-0383Selatogrel, 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.Lydie CrescenceMarkus KrambergMartine BaumannMarkus ReySebastien RouxLaurence Panicot-DuboisChristophe DuboisMarkus A. RiedererMDPI AGarticleP2Y12 receptorplateletsthrombosishaemostasisthrombus dissolutionMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5349, p 5349 (2021) |
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P2Y12 receptor platelets thrombosis haemostasis thrombus dissolution Medicine R |
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P2Y12 receptor platelets thrombosis haemostasis thrombus dissolution Medicine R 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
p2y12 receptor antagonist selatogrel dissolves preformed platelet thrombi in vivo |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/0e5782d9d234401d99bb89284b6efdf4 |
| work_keys_str_mv |
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