Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels

Abstract Circulating extracellular vesicles (EVs) regulate signaling pathways via receptor-ligand interactions and content delivery, after attachment or internalization by endothelial cells. However, they originate from diverse cell populations and are heterogeneous in composition. To determine the...

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Autores principales:	Zsolt Bagi, Yvonne Couch, Zuzana Broskova, Francisco Perez-Balderas, Tianrong Yeo, Simon Davis, Roman Fischer, Nicola R. Sibson, Benjamin G. Davis, Daniel C. Anthony
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80e085b716b4414290975bfd434f3a27
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spelling	oai:doaj.org-article:80e085b716b4414290975bfd434f3a272021-12-02T15:09:24ZExtracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels10.1038/s41598-019-52127-32045-2322https://doaj.org/article/80e085b716b4414290975bfd434f3a272019-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-52127-3https://doaj.org/toc/2045-2322Abstract Circulating extracellular vesicles (EVs) regulate signaling pathways via receptor-ligand interactions and content delivery, after attachment or internalization by endothelial cells. However, they originate from diverse cell populations and are heterogeneous in composition. To determine the effects of specific surface molecules, the use of synthetic EV mimetics permits the study of specific EV receptor-ligand interactions. Here, we used endogenous EVs derived from the circulation of rats, as well as ligand-decorated synthetic microparticles (MPs) to examine the role of integrin αvβ3 in platelet adhesion under flow in structurally intact cerebral arteries. At an intraluminal pressure of 50 mmHg and flow rate of 10 µl/min, platelets were delivered to the artery lumen and imaged with whole-field fluorescent microscopy. Under basal conditions very few platelets bound to the endothelium. However, adhesion events were markedly increased following the introduction of arginine-glycine-aspartate (RGD)-labelled synthetic MPs or endogenously-derived EVs from experimental stroke animals carrying excess RGD proteins, including vitronectin, CD40-ligand and thrombospondin-1. These data, which were generated in a dynamic and physiologically relevant system, demonstrate the importance of vesicle-carried RGD ligands in platelet adherence to the cerebrovascular endothelium and highlight the ability of synthetic EVs to isolate and identify key components of the molecular handshake between EVs and their targets.Zsolt BagiYvonne CouchZuzana BroskovaFrancisco Perez-BalderasTianrong YeoSimon DavisRoman FischerNicola R. SibsonBenjamin G. DavisDaniel C. AnthonyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zsolt Bagi Yvonne Couch Zuzana Broskova Francisco Perez-Balderas Tianrong Yeo Simon Davis Roman Fischer Nicola R. Sibson Benjamin G. Davis Daniel C. Anthony Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
description	Abstract Circulating extracellular vesicles (EVs) regulate signaling pathways via receptor-ligand interactions and content delivery, after attachment or internalization by endothelial cells. However, they originate from diverse cell populations and are heterogeneous in composition. To determine the effects of specific surface molecules, the use of synthetic EV mimetics permits the study of specific EV receptor-ligand interactions. Here, we used endogenous EVs derived from the circulation of rats, as well as ligand-decorated synthetic microparticles (MPs) to examine the role of integrin αvβ3 in platelet adhesion under flow in structurally intact cerebral arteries. At an intraluminal pressure of 50 mmHg and flow rate of 10 µl/min, platelets were delivered to the artery lumen and imaged with whole-field fluorescent microscopy. Under basal conditions very few platelets bound to the endothelium. However, adhesion events were markedly increased following the introduction of arginine-glycine-aspartate (RGD)-labelled synthetic MPs or endogenously-derived EVs from experimental stroke animals carrying excess RGD proteins, including vitronectin, CD40-ligand and thrombospondin-1. These data, which were generated in a dynamic and physiologically relevant system, demonstrate the importance of vesicle-carried RGD ligands in platelet adherence to the cerebrovascular endothelium and highlight the ability of synthetic EVs to isolate and identify key components of the molecular handshake between EVs and their targets.
format	article
author	Zsolt Bagi Yvonne Couch Zuzana Broskova Francisco Perez-Balderas Tianrong Yeo Simon Davis Roman Fischer Nicola R. Sibson Benjamin G. Davis Daniel C. Anthony
author_facet	Zsolt Bagi Yvonne Couch Zuzana Broskova Francisco Perez-Balderas Tianrong Yeo Simon Davis Roman Fischer Nicola R. Sibson Benjamin G. Davis Daniel C. Anthony
author_sort	Zsolt Bagi
title	Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
title_short	Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
title_full	Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
title_fullStr	Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
title_full_unstemmed	Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
title_sort	extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/80e085b716b4414290975bfd434f3a27
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Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels

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