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Platelet-derived extracellular vesicles express NADPH oxidase-1 (Nox-1), generate superoxide and modulate platelet function

Gaspar, R. S., Ferreira, P., Mitchell, J. L., Pula, G. and Gibbins, J. M. ORCID: (2021) Platelet-derived extracellular vesicles express NADPH oxidase-1 (Nox-1), generate superoxide and modulate platelet function. Free Radical Biology and Medicine, 165. pp. 395-400. ISSN 0891-5849

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To link to this item DOI: 10.1016/j.freeradbiomed.2021.01.051


Background: Platelets release platelet-derived extracellular vesicles (PDEVs) upon activation – in a process that is regulated by generation of reactive oxygen species (ROS). Platelet NADPH oxidase-1 (Nox-1) contributes to ROS generation and thrombus formation downstream of the collagen receptor GPVI. Objectives: We aimed to investigate whether PDEVs contain Nox-1 and whether this is relevant for PDEV-induced platelet activation. Methods: PDEVs were isolated through serial centrifugation after platelet activation with thrombin receptor agonist TRAP-6 (activated PDEVs) or in the absence of agonist (resting PDEVs). The physical properties of PDEVs were analysed through nanoparticle tracking analysis. Nox-1 levels, fibrinogen binding and P-selectin exposure were measured using flow cytometry, and protein levels quantified by immunoblot analysis. ROS were quantified using DCF fluorescence and electron paramagnetic resonance. Results: Nox-1 was found to be increased on the platelet outer membrane upon activation and was found to be present in PDEVs. PDEVs induced platelet activation, while co-addition of GPVI agonist collagen-related peptide (CRP) did not potentiate this response. PDEVs were shown to be able to generate superoxide in a process at least partially mediated by Nox- 1, while Nox-1 inhibition with ML171 (also known as 2-APT) did not influence PDEV production. Finally, inhibition of Nox-1 abrogated PDEV-mediated platelet activation. Conclusions: PDEVs are able to generate superoxide, bind to and activate platelets in a process mediated by Nox-1. These data provide novel mechanisms by which Nox-1 potentiates platelet responses, thus proposing Nox-1 inhibition as a feasible strategy to treat and prevent thrombotic diseases.

Item Type:Article
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:95971
Uncontrolled Keywords:Platelets, extracellular vesicles, NADPH oxidase, platelet activation, redox biology


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