Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo

Autores
Mena, Hebe Agustina; Zubiry, Paula Romina; Dizier, Blandine; Mignon, Virginie; Parborell, Maria Fernanda Agustina; Schattner, Mirta Ana; Boisson Vidal, Catherine; Negrotto, Soledad
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow–derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony–orming cells (ECFCs). Approach and Results: C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystal–induced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair. Conclusions: Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy.
Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Dizier, Blandine. Inserm; Francia. Universite de Paris; Francia
Fil: Mignon, Virginie. Inserm; Francia. Universite de Paris; Francia
Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Boisson Vidal, Catherine. Inserm; Francia. Universite de Paris; Francia
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
ENDOTHELIAL COLONY FORMING CELLS
CERMIDE 1 PHOSPHATE
VASCULOGENESIS
PROANGIOGENIC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/108399
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/108399
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In VivoMena, Hebe AgustinaZubiry, Paula RominaDizier, BlandineMignon, VirginieParborell, Maria Fernanda AgustinaSchattner, Mirta AnaBoisson Vidal, CatherineNegrotto, SoledadENDOTHELIAL COLONY FORMING CELLSCERMIDE 1 PHOSPHATEVASCULOGENESISPROANGIOGENIChttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Objective: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow–derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony–orming cells (ECFCs). Approach and Results: C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystal–induced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair. Conclusions: Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy.Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Dizier, Blandine. Inserm; Francia. Universite de Paris; FranciaFil: Mignon, Virginie. Inserm; Francia. Universite de Paris; FranciaFil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Boisson Vidal, Catherine. Inserm; Francia. Universite de Paris; FranciaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaLippincott Williams2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/108399Mena, Hebe Agustina; Zubiry, Paula Romina; Dizier, Blandine; Mignon, Virginie; Parborell, Maria Fernanda Agustina; et al.; Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 8-20191079-5642CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/ATVBAHA.119.312766info:eu-repo/semantics/altIdentifier/doi/10.1161/ATVBAHA.119.312766info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:08Zoai:ri.conicet.gov.ar:11336/108399instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:46:08.726CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
title Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
spellingShingle Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
Mena, Hebe Agustina
ENDOTHELIAL COLONY FORMING CELLS
CERMIDE 1 PHOSPHATE
VASCULOGENESIS
PROANGIOGENIC
title_short Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
title_full Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
title_fullStr Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
title_full_unstemmed Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
title_sort Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo
dc.creator.none.fl_str_mv Mena, Hebe Agustina
Zubiry, Paula Romina
Dizier, Blandine
Mignon, Virginie
Parborell, Maria Fernanda Agustina
Schattner, Mirta Ana
Boisson Vidal, Catherine
Negrotto, Soledad
author Mena, Hebe Agustina
author_facet Mena, Hebe Agustina
Zubiry, Paula Romina
Dizier, Blandine
Mignon, Virginie
Parborell, Maria Fernanda Agustina
Schattner, Mirta Ana
Boisson Vidal, Catherine
Negrotto, Soledad
author_role author
author2 Zubiry, Paula Romina
Dizier, Blandine
Mignon, Virginie
Parborell, Maria Fernanda Agustina
Schattner, Mirta Ana
Boisson Vidal, Catherine
Negrotto, Soledad
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ENDOTHELIAL COLONY FORMING CELLS
CERMIDE 1 PHOSPHATE
VASCULOGENESIS
PROANGIOGENIC
topic ENDOTHELIAL COLONY FORMING CELLS
CERMIDE 1 PHOSPHATE
VASCULOGENESIS
PROANGIOGENIC
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow–derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony–orming cells (ECFCs). Approach and Results: C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystal–induced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair. Conclusions: Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy.
Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Zubiry, Paula Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Dizier, Blandine. Inserm; Francia. Universite de Paris; Francia
Fil: Mignon, Virginie. Inserm; Francia. Universite de Paris; Francia
Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Boisson Vidal, Catherine. Inserm; Francia. Universite de Paris; Francia
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Objective: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow–derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony–orming cells (ECFCs). Approach and Results: C1P protected ECFC from TNFα (tumor necrosis factor-α)-induced and monosodium urate crystal–induced death and acted as a potent chemoattractant factor through the activation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and AKT pathways. C1P treatment enhanced ECFC adhesion to collagen type I, an effect that was prevented by β1 integrin blockade, and to mature endothelial cells, which was mediated by the E-selectin/CD44 axis. ECFC proliferation and cord-like structure formation were also increased by C1P, as well as vascularization of gel plug implants loaded or not with ECFC. In a murine model of hindlimb ischemia, local administration of C1P alone promoted blood perfusion and reduced necrosis in the ischemic muscle. Additionally, the beneficial effects of ECFC infusion after ischemia were amplified by C1P pretreatment, resulting in a further and significant enhancement of leg reperfusion and muscle repair. Conclusions: Our findings suggest that C1P may have therapeutic relevance in ischemic disorders, improving tissue repair by itself, or priming ECFC angiogenic responses such as chemotaxis, adhesion, proliferation, and tubule formation, which result in a better outcome of ECFC-based therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/108399
Mena, Hebe Agustina; Zubiry, Paula Romina; Dizier, Blandine; Mignon, Virginie; Parborell, Maria Fernanda Agustina; et al.; Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 8-2019
1079-5642
CONICET Digital
CONICET
url http://hdl.handle.net/11336/108399
identifier_str_mv Mena, Hebe Agustina; Zubiry, Paula Romina; Dizier, Blandine; Mignon, Virginie; Parborell, Maria Fernanda Agustina; et al.; Ceramide 1-Phosphate Protects Endothelial Colony Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 8-2019
1079-5642
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/ATVBAHA.119.312766
info:eu-repo/semantics/altIdentifier/doi/10.1161/ATVBAHA.119.312766
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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