Towards the Therapeutic Use of TSP-1 (Thrombospondin-1)/CD47 Targeting TAX2 Peptide as an Antithrombotic Agent.
Fiche publication
Date publication
novembre 2020
Journal
Arteriosclerosis, thrombosis, and vascular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DEDIEU Stéphane, Pr MARTINY Laurent
Tous les auteurs :
Jeanne A, Sarazin T, Charlé M, Kawecki C, Kauskot A, Hedtke T, Schmelzer CEH, Martiny L, Maurice P, Dedieu S
Lien Pubmed
Résumé
TSP-1 (thrombospondin 1) is one of the most expressed proteins in platelet α-granules and plays an important role in the regulation of hemostasis and thrombosis. Interaction of released TSP-1 with CD47 membrane receptor has been shown to regulate major events leading to thrombus formation, for example, platelet adhesion to vascular endothelium, nitric oxide/cGMP signaling, platelet activation as well as aggregation. Therefore, targeting TSP-1:CD47 axis may represent a promising antithrombotic strategy. Approach and Results: A CD47-derived cyclic peptide was engineered, namely TAX2, that targets TSP-1 and selectively prevents TSP-1:CD47 interaction. Here, we demonstrate for the first time that TAX2 peptide strongly decreases platelet aggregation and interaction with collagen under arterial shear conditions. TAX2 also delays time for complete thrombotic occlusion in 2 mouse models of arterial thrombosis following chemical injury, while mice recapitulate TAX2 effects. Importantly, TAX2 administration is not associated with increased bleeding risk or modification of hematologic parameters.
Mots clés
anticoagulants, cardiovascular diseases, platelet aggregation, thrombosis, thrombospondin 1
Référence
Arterioscler Thromb Vasc Biol. 2020 Nov 24;:ATVBAHA120314571