Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry

Abstract Endothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic...

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Autores principales:	Wolfgang Holnthoner, Cornelia Bonstingl, Carina Hromada, Severin Muehleder, Johannes Zipperle, Stefan Stojkovic, Heinz Redl, Johann Wojta, Herbert Schöchl, Johannes Grillari, Sylvia Weilner, Christoph J. Schlimp
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b59d295e2d64436eb0f3caf173c50868
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spelling	oai:doaj.org-article:b59d295e2d64436eb0f3caf173c508682021-12-02T11:52:23ZEndothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry10.1038/s41598-017-03159-02045-2322https://doaj.org/article/b59d295e2d64436eb0f3caf173c508682017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03159-0https://doaj.org/toc/2045-2322Abstract Endothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic clotting time. This effect was reversed with an anti-tissue factor antibody. Here, we aimed to investigate whether tissue factor (TF) was released by endothelial-derived extracellular vesicles (EVs) and which portion of the released vesicles displays the most prominent procoagulant properties. After stimulation of ECs with tumor-necrosis factor-α (TNF-α) the supernatants of EC cultures were subjected to differential centrifugation steps to collect larger and smaller EVs which were then characterised by nanoparticle tracking analysis (NTA) and flow cytometry. Mixed with fresh human blood and analysed by thromboelastometry EVs exerted a significant procoagulant stimulus, which could be partly reversed by addition of an anti-TF antibody. Moreover, TF activity was confirmed in the centrifuged fractions. In summary, our results provide evidence of the procoagulant potential of smaller and larger endothelial-derived EV fractions detected by thromboelastometry. The observed effect is most likely due to the release of TF-bearing EVs of different dimensions, which are released upon TNF-α stimulation of endothelial cell cultures.Wolfgang HolnthonerCornelia BonstinglCarina HromadaSeverin MuehlederJohannes ZipperleStefan StojkovicHeinz RedlJohann WojtaHerbert SchöchlJohannes GrillariSylvia WeilnerChristoph J. SchlimpNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wolfgang Holnthoner Cornelia Bonstingl Carina Hromada Severin Muehleder Johannes Zipperle Stefan Stojkovic Heinz Redl Johann Wojta Herbert Schöchl Johannes Grillari Sylvia Weilner Christoph J. Schlimp Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
description	Abstract Endothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic clotting time. This effect was reversed with an anti-tissue factor antibody. Here, we aimed to investigate whether tissue factor (TF) was released by endothelial-derived extracellular vesicles (EVs) and which portion of the released vesicles displays the most prominent procoagulant properties. After stimulation of ECs with tumor-necrosis factor-α (TNF-α) the supernatants of EC cultures were subjected to differential centrifugation steps to collect larger and smaller EVs which were then characterised by nanoparticle tracking analysis (NTA) and flow cytometry. Mixed with fresh human blood and analysed by thromboelastometry EVs exerted a significant procoagulant stimulus, which could be partly reversed by addition of an anti-TF antibody. Moreover, TF activity was confirmed in the centrifuged fractions. In summary, our results provide evidence of the procoagulant potential of smaller and larger endothelial-derived EV fractions detected by thromboelastometry. The observed effect is most likely due to the release of TF-bearing EVs of different dimensions, which are released upon TNF-α stimulation of endothelial cell cultures.
format	article
author	Wolfgang Holnthoner Cornelia Bonstingl Carina Hromada Severin Muehleder Johannes Zipperle Stefan Stojkovic Heinz Redl Johann Wojta Herbert Schöchl Johannes Grillari Sylvia Weilner Christoph J. Schlimp
author_facet	Wolfgang Holnthoner Cornelia Bonstingl Carina Hromada Severin Muehleder Johannes Zipperle Stefan Stojkovic Heinz Redl Johann Wojta Herbert Schöchl Johannes Grillari Sylvia Weilner Christoph J. Schlimp
author_sort	Wolfgang Holnthoner
title	Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
title_short	Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
title_full	Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
title_fullStr	Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
title_full_unstemmed	Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
title_sort	endothelial cell-derived extracellular vesicles size-dependently exert procoagulant activity detected by thromboelastometry
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b59d295e2d64436eb0f3caf173c50868
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Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry

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