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Article Dans Une Revue Journal of Thrombosis and Haemostasis Année : 2024

Extracellular vesicles from activated platelets possess a phospholipid-rich biomolecular profile and enhance prothrombinase activity

Eduarda Guerreiro
  • Fonction : Auteur
Samantha Swamy
  • Fonction : Auteur
Nadezhda Latysheva
  • Fonction : Auteur
Bjarne Østerud
  • Fonction : Auteur
Stephanie Bonneau
Andrey Kuzmin
  • Fonction : Auteur
Paras Prasad
  • Fonction : Auteur
John-Bjarne Hansen
  • Fonction : Auteur
Olav Gaute Hellesø
  • Fonction : Auteur
Omri Snir
  • Fonction : Auteur

Résumé

Background Extracellular vesicles (EVs), in particular those derived from activated platelets, are associated with a risk of future venous thromboembolism (VTE). Objectives Study the biomolecular profile and function characteristics of EVs from control (unstimulated) and activated platelets. Methods Biomolecular profiling of single- or very-few- (1 to 4) platelet-EVs (control/stimulated) was carried by Raman Tweezers Microspectroscopy (RTM). The effects of such EVs on the coagulation system were comprehensively studied. Results RTM of platelet-EVs followed by Biomolecular Component Analysis revealed for the first time three subsets of EVs: (i) protein-rich, (ii) protein/lipid-rich, and (iii) lipid-rich. EVs from control platelets presented a heterogeneous biomolecular profile, with protein-rich EVs being the main subset (58.7±3.5%). Notably, the protein-rich subset may contain a minor contribution from other extracellular particles, including protein aggregates. In contrast, EVs from activated platelets were more homogeneous, dominated by the protein/lipid-rich subset (>85%), and enriched in phospholipids. Functionally, EVs from activated platelets increased thrombin generation by 52.4% and shortened plasma coagulation time by 34.6±10.0% in comparison to 18.6±13.9% mediated by EVs from control platelets, p=0.015. The increased procoagulant activity was predominantly mediated by phosphatidylserine (PS). Detailed investigation showed that EVs from activated platelets increased the activity of the prothrombinase complex (FVa:FXa:FII) by more than 6-fold. Conclusion Our study reports a novel quantitative biomolecular characterization of platelet-EVs, possessing a homogenous and phospholipid-enriched profile in response to platelet activation. Such characteristics are accompanied with an increased PS-dependent procoagulant activity. Further investigation of a possible role of platelet-EVs in the pathogenesis of VTE is warranted.
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hal-04420532 , version 1 (29-04-2024)

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Eduarda Guerreiro, Sergei Kruglik, Samantha Swamy, Nadezhda Latysheva, Bjarne Østerud, et al.. Extracellular vesicles from activated platelets possess a phospholipid-rich biomolecular profile and enhance prothrombinase activity. Journal of Thrombosis and Haemostasis, 2024, 22 (5), pp.1463-1474. ⟨10.1016/j.jtha.2024.01.004⟩. ⟨hal-04420532⟩
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