Fiche publication
Date publication
décembre 2025
Journal
Biophysical journal
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MANGIN Pierre
Tous les auteurs :
Yakusheva AA, Megalinskii AD, Bourdon C, Eckly A, Shibeko AM, Ataullakhanov FI, Nechipurenko DY, Mangin PH, Panteleev MA
Lien Pubmed
Résumé
Platelet accumulation following non-penetrating vessel injury exhibits a characteristic kinetic profile with initial formation of a large thrombus that subsequently shrinks to a smaller aggregate covering the injury. While the molecular mechanisms of platelet aggregation are well characterized, the physiological relevance of this transient large thrombus formation has never been studied. Using a low concentration FeCl model of the carotid artery we confirmed that arterial thrombus formation presented a peak-shape kinetic and ended by the formation of a small stable remaining aggregate. Further characterization of this remnant with electron microscopy and immunofluorescence indicated that it was composed of the highly activated platelets and was particularly rich in fibrin. Combining in silico and in vivo approaches we investigated the possible significance of the initial accumulation of an apparently superfluous number of platelets. Both the numerical model and experiments with thrombocytopenic mice indicated that the thrombus with the height of more than 10-20% of the vessel lumen provided a shelter to facilitate intra-thrombus coagulation even under high shear blood flow and it was essential to generate sufficient amounts of thrombin to create the underlying fibrin-rich patch. The critical size of thrombus required for such protection in silico depended on such parameters as injury length, tissue factor density and shear rate. In agreement with the computational model, our in vivo data revealed that P2Y or αIIbβ3 blockers administered to mice during the build-up of an initial sub-occlusive thrombus inhibited the formation of fibrin in the remaining aggregate, emphasizing the importance of thrombus for intra-thrombus coagulation. We propose that the physiological role of the initial formation of a large enough platelet thrombus upon injury is to provide a protective environment allowing coagulation to proceed even at high shear rates and low tissue factor densities, and ultimately produce a stable fibrin-rich aggregate.
Référence
Biophys J. 2025 12 23;:
