Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia

Abstract Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodel...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Claudia Cavallari, Andrea Ranghino, Marta Tapparo, Massimo Cedrino, Federico Figliolini, Cristina Grange, Valentina Giannachi, Paolo Garneri, Maria Chiara Deregibus, Federica Collino, Pietro Rispoli, Giovanni Camussi, Maria Felice Brizzi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c2b6e76c2a147b9aa40a90b1fce12aa
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6c2b6e76c2a147b9aa40a90b1fce12aa
record_format	dspace
spelling	oai:doaj.org-article:6c2b6e76c2a147b9aa40a90b1fce12aa2021-12-02T12:31:50ZSerum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia10.1038/s41598-017-08250-02045-2322https://doaj.org/article/6c2b6e76c2a147b9aa40a90b1fce12aa2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08250-0https://doaj.org/toc/2045-2322Abstract Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute hind limb ischemia. e-sEV angiogenic proteomic and transcriptomic analyses show a positive correlation with matrix-metalloproteinase activation and extracellular matrix organization, cytokine and chemokine signaling pathways, Insulin-like Growth Factor and platelet pathways, and Vascular Endothelial Growth Factor signaling. A discrete gene signature, which highlights differences in e-sEV and ineffective-EV biological activity, was identified using gene ontology (GO) functional analysis. An enrichment of genes associated with the Transforming Growth Factor beta 1 (TGFβ1) signaling cascade is associated with e-sEV administration but not with ineffective-EVs. Chromatin immunoprecipitation analysis on the inhibitor of DNA binding I (ID1) promoter region, and the knock-down of small mother against decapentaplegic (SMAD)1–5 proteins confirmed GO functional analyses. This study demonstrates sEV pro-angiogenic activity, validates a simple, sEV pro-angiogenic assay which predicts their biological activity in vivo, and identifies the TGFβ1 cascade as a relevant mediator. We propose serum as a readily available source of EVs for therapeutic purposes.Claudia CavallariAndrea RanghinoMarta TapparoMassimo CedrinoFederico FiglioliniCristina GrangeValentina GiannachiPaolo GarneriMaria Chiara DeregibusFederica CollinoPietro RispoliGiovanni CamussiMaria Felice BrizziNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Cavallari Andrea Ranghino Marta Tapparo Massimo Cedrino Federico Figliolini Cristina Grange Valentina Giannachi Paolo Garneri Maria Chiara Deregibus Federica Collino Pietro Rispoli Giovanni Camussi Maria Felice Brizzi Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
description	Abstract Serum is an abundant and accessible source of circulating extracellular vesicles (EVs). Serum-EV (sEV) pro-angiogenic capability and mechanisms are herein analyzed using an in vitro assay which predicts sEV angiogenic potential in vivo. Effective sEVs (e-sEVs) also improved vascular remodeling and prevented muscle damage in a mouse model of acute hind limb ischemia. e-sEV angiogenic proteomic and transcriptomic analyses show a positive correlation with matrix-metalloproteinase activation and extracellular matrix organization, cytokine and chemokine signaling pathways, Insulin-like Growth Factor and platelet pathways, and Vascular Endothelial Growth Factor signaling. A discrete gene signature, which highlights differences in e-sEV and ineffective-EV biological activity, was identified using gene ontology (GO) functional analysis. An enrichment of genes associated with the Transforming Growth Factor beta 1 (TGFβ1) signaling cascade is associated with e-sEV administration but not with ineffective-EVs. Chromatin immunoprecipitation analysis on the inhibitor of DNA binding I (ID1) promoter region, and the knock-down of small mother against decapentaplegic (SMAD)1–5 proteins confirmed GO functional analyses. This study demonstrates sEV pro-angiogenic activity, validates a simple, sEV pro-angiogenic assay which predicts their biological activity in vivo, and identifies the TGFβ1 cascade as a relevant mediator. We propose serum as a readily available source of EVs for therapeutic purposes.
format	article
author	Claudia Cavallari Andrea Ranghino Marta Tapparo Massimo Cedrino Federico Figliolini Cristina Grange Valentina Giannachi Paolo Garneri Maria Chiara Deregibus Federica Collino Pietro Rispoli Giovanni Camussi Maria Felice Brizzi
author_facet	Claudia Cavallari Andrea Ranghino Marta Tapparo Massimo Cedrino Federico Figliolini Cristina Grange Valentina Giannachi Paolo Garneri Maria Chiara Deregibus Federica Collino Pietro Rispoli Giovanni Camussi Maria Felice Brizzi
author_sort	Claudia Cavallari
title	Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
title_short	Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
title_full	Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
title_fullStr	Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
title_full_unstemmed	Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
title_sort	serum-derived extracellular vesicles (evs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6c2b6e76c2a147b9aa40a90b1fce12aa
work_keys_str_mv	AT claudiacavallari serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT andrearanghino serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT martatapparo serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT massimocedrino serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT federicofigliolini serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT cristinagrange serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT valentinagiannachi serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT paologarneri serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT mariachiaraderegibus serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT federicacollino serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT pietrorispoli serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT giovannicamussi serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia AT mariafelicebrizzi serumderivedextracellularvesiclesevsimpactonvascularremodelingandpreventmuscledamageinacutehindlimbischemia
_version_	1718394283208212480

Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia

Ejemplares similares