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

  • J Thromb Haemost. 2024 Jan 22:S1538-7836(24)00041-2. doi: 10.1016/j.jtha.2024.01.004.
Eduarda M Guerreiro  1 ,  Sergei G Kruglik  2 ,  Samantha Swamy  1 ,  Nadezhda Latysheva  1 ,  Bjarne Østerud  1 ,  Jean-Michel Guigner  3 ,  Franck Sureau  4 ,  Stephanie Bonneau  4 ,  Andrey N Kuzmin  5 ,  Paras N Prasad  5 ,  John-Bjarne Hansen  6 ,  Olav Gaute Hellesø  7 ,  Omri Snir  8
Affiliations
  • 1. Thrombosis Research Group (TREC), Institute of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
  • 2. Laboratoire Jean Perrin, Institut de Biologie Paris-Seine, Sorbonne Université, CNRS, 75005 Paris, France. Electronic address: [email protected].
  • 3. L'Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, Sorbonne Université, CNRS, IRD, MNHN, 75005 Paris, France.
  • 4. Laboratoire Jean Perrin, Institut de Biologie Paris-Seine, Sorbonne Université, CNRS, 75005 Paris, France.
  • 5. Institute for Lasers, Photonics and Biophotonics and the Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
  • 6. Thrombosis Research Group (TREC), Institute of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
  • 7. Department of Physics and Technology, UiT- The Arctic University of Norway, Tromsø, Norway.
  • 8. Thrombosis Research Group (TREC), Institute of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway. Electronic address: [email protected].
PMID: 38266680 DOI: 10.1016/j.jtha.2024.01.004
Abstract

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.

Keywords
Biomolecular composition; Raman Tweezers Microspectroscopy; platelet extracellular vesicles; prothrombinase activity; venous thromboembolism.
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