Platelet-released extracellular vesicles: the effects of thrombin activation

Platelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to thrombus formation. However, pEV composition...

Descripción completa

Detalles Bibliográficos
Autores: Suades, R, Padro, T, Vilahur, G, Badimon, L
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p8118
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8118
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126234882&doi=10.1007%2fs00018-022-04222-4&partnerID=40&md5=d41529e8e17e436a57aac0cdeb954b0e
Access Level:acceso abierto
Palabra clave:Atherosclerosis
Extracellular vesicles
Microvesicles
Platelets
Thrombin
Thrombosis
id ES_cd22574eae716a4d22fcf1e5ce698749
oai_identifier_str oai:iibsantpau.fundanetsuite.com:p8118
network_acronym_str ES
network_name_str España
repository_id_str
spelling Platelet-released extracellular vesicles: the effects of thrombin activationSuades, RPadro, TVilahur, GBadimon, LAtherosclerosisExtracellular vesiclesMicrovesiclesPlateletsThrombinThrombosisPlatelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to thrombus formation. However, pEV composition remains poorly defined. Indeed, pEV quality and type, rather than quantity, may be relevant in intravascular cross-talk with either circulating or vascular cells. We aimed to define the phenotypic characteristics of pEVs released spontaneously and those induced by thrombin activation to better understand their role in disease dissemination. pEVs obtained from washed platelets from healthy donor blood were characterized by flow cytometry. pEVs from thrombin-activated platelets (T-pEVs) showed higher levels of P-selectin and active form of glycoprotein IIb/IIIa than baseline non-activated platelets (B-pEVs). Following mass spectrometry-based differential proteomic analysis, significant changes in the abundance of proteins secreted in T-pEVs compared to B-pEVs were found. These differential proteins were involved in coagulation, adhesion, cytoskeleton, signal transduction, metabolism, and vesicle-mediated transport. Interestingly, release of proteins relevant for cell adhesion, intrinsic pathway coagulation, and platelet activation signalling was significantly modified by thrombin stimulation. A novel pEV-associated protein (protocadherin-alpha 4) was found to be significantly reduced in T-pEVs showing a shift towards increased expression in the membranes of activated platelets. In summary, platelet activation induced by thrombin triggers the shedding of pEVs with a complex proteomic pattern rich in procoagulant and proadhesive proteins. Crosstalk with other vascular and blood cells in a paracrine regulatory mode could extend the prothrombotic signalling as well as promote proteostasic changes in other cellular types.SPRINGER BASEL AG2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8118https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126234882&doi=10.1007%2fs00018-022-04222-4&partnerID=40&md5=d41529e8e17e436a57aac0cdeb954b0eCELLULAR AND MOLECULAR LIFE SCIENCESISSN: 1420682XISSNe: 14209071reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p81182026-06-14T12:41:47Z
dc.title.none.fl_str_mv Platelet-released extracellular vesicles: the effects of thrombin activation
title Platelet-released extracellular vesicles: the effects of thrombin activation
spellingShingle Platelet-released extracellular vesicles: the effects of thrombin activation
Suades, R
Atherosclerosis
Extracellular vesicles
Microvesicles
Platelets
Thrombin
Thrombosis
title_short Platelet-released extracellular vesicles: the effects of thrombin activation
title_full Platelet-released extracellular vesicles: the effects of thrombin activation
title_fullStr Platelet-released extracellular vesicles: the effects of thrombin activation
title_full_unstemmed Platelet-released extracellular vesicles: the effects of thrombin activation
title_sort Platelet-released extracellular vesicles: the effects of thrombin activation
dc.creator.none.fl_str_mv Suades, R
Padro, T
Vilahur, G
Badimon, L
author Suades, R
author_facet Suades, R
Padro, T
Vilahur, G
Badimon, L
author_role author
author2 Padro, T
Vilahur, G
Badimon, L
author2_role author
author
author
dc.subject.none.fl_str_mv Atherosclerosis
Extracellular vesicles
Microvesicles
Platelets
Thrombin
Thrombosis
topic Atherosclerosis
Extracellular vesicles
Microvesicles
Platelets
Thrombin
Thrombosis
description Platelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to thrombus formation. However, pEV composition remains poorly defined. Indeed, pEV quality and type, rather than quantity, may be relevant in intravascular cross-talk with either circulating or vascular cells. We aimed to define the phenotypic characteristics of pEVs released spontaneously and those induced by thrombin activation to better understand their role in disease dissemination. pEVs obtained from washed platelets from healthy donor blood were characterized by flow cytometry. pEVs from thrombin-activated platelets (T-pEVs) showed higher levels of P-selectin and active form of glycoprotein IIb/IIIa than baseline non-activated platelets (B-pEVs). Following mass spectrometry-based differential proteomic analysis, significant changes in the abundance of proteins secreted in T-pEVs compared to B-pEVs were found. These differential proteins were involved in coagulation, adhesion, cytoskeleton, signal transduction, metabolism, and vesicle-mediated transport. Interestingly, release of proteins relevant for cell adhesion, intrinsic pathway coagulation, and platelet activation signalling was significantly modified by thrombin stimulation. A novel pEV-associated protein (protocadherin-alpha 4) was found to be significantly reduced in T-pEVs showing a shift towards increased expression in the membranes of activated platelets. In summary, platelet activation induced by thrombin triggers the shedding of pEVs with a complex proteomic pattern rich in procoagulant and proadhesive proteins. Crosstalk with other vascular and blood cells in a paracrine regulatory mode could extend the prothrombotic signalling as well as promote proteostasic changes in other cellular types.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8118
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126234882&doi=10.1007%2fs00018-022-04222-4&partnerID=40&md5=d41529e8e17e436a57aac0cdeb954b0e
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8118
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126234882&doi=10.1007%2fs00018-022-04222-4&partnerID=40&md5=d41529e8e17e436a57aac0cdeb954b0e
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGER BASEL AG
publisher.none.fl_str_mv SPRINGER BASEL AG
dc.source.none.fl_str_mv CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN: 1420682X
ISSNe: 14209071
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419782697123840
score 15.81155

Similares en LA Referencia