Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

Autores
Ahmad, Shakil; Hewett, Peter W.; Fujisawa, Takeshi; Sissaoui, Samir; Cai, Meng; Gueron, Geraldine; Al Ani, Bahjat; Cudmore, Melissa; Faraz Ahmed, S.; Wong, Michael K. K.; Wegiel, Barbara; Otterbein, Leo E.; Vítek, Libor; Ramma, Wenda; Wang, Keqing; Ahmed, Asif
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.
Fil: Ahmad, Shakil. Aston University; Reino Unido
Fil: Hewett, Peter W.. University Of Birmingham; Reino Unido
Fil: Fujisawa, Takeshi. University Of Birmingham; Reino Unido
Fil: Sissaoui, Samir. University Of Birmingham; Reino Unido
Fil: Cai, Meng. Aston University; Reino Unido
Fil: Gueron, Geraldine. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Al Ani, Bahjat. University Of Birmingham; Reino Unido
Fil: Cudmore, Melissa. University Of Birmingham; Reino Unido
Fil: Faraz Ahmed, S.. University of Liverpool; Reino Unido
Fil: Wong, Michael K. K.. University Of Southern California; Estados Unidos
Fil: Wegiel, Barbara. Harvard Medical School; Estados Unidos
Fil: Otterbein, Leo E.. Aston University; Reino Unido. Harvard Medical School; Estados Unidos
Fil: Vítek, Libor. Charles University; República Checa
Fil: Ramma, Wenda. Harvard Medical School; Estados Unidos
Fil: Wang, Keqing. Aston University; Reino Unido
Fil: Ahmed, Asif. Aston University; Reino Unido
Materia
Angiogenesis
Carbon Monoxide
Endothelial Cells
Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-2
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:11336/36887
Acceder
id CONICETDig_7bf7bf8b6c11c2ee09f18ed18eac7286
oai_identifier_str oai:ri.conicet.gov.ar:11336/36887
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylationAhmad, ShakilHewett, Peter W.Fujisawa, TakeshiSissaoui, SamirCai, MengGueron, GeraldineAl Ani, BahjatCudmore, MelissaFaraz Ahmed, S.Wong, Michael K. K.Wegiel, BarbaraOtterbein, Leo E.Vítek, LiborRamma, WendaWang, KeqingAhmed, AsifAngiogenesisCarbon MonoxideEndothelial CellsVascular Endothelial Growth FactorVascular Endothelial Growth Factor Receptor-2https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.Fil: Ahmad, Shakil. Aston University; Reino UnidoFil: Hewett, Peter W.. University Of Birmingham; Reino UnidoFil: Fujisawa, Takeshi. University Of Birmingham; Reino UnidoFil: Sissaoui, Samir. University Of Birmingham; Reino UnidoFil: Cai, Meng. Aston University; Reino UnidoFil: Gueron, Geraldine. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Al Ani, Bahjat. University Of Birmingham; Reino UnidoFil: Cudmore, Melissa. University Of Birmingham; Reino UnidoFil: Faraz Ahmed, S.. University of Liverpool; Reino UnidoFil: Wong, Michael K. K.. University Of Southern California; Estados UnidosFil: Wegiel, Barbara. Harvard Medical School; Estados UnidosFil: Otterbein, Leo E.. Aston University; Reino Unido. Harvard Medical School; Estados UnidosFil: Vítek, Libor. Charles University; República ChecaFil: Ramma, Wenda. Harvard Medical School; Estados UnidosFil: Wang, Keqing. Aston University; Reino UnidoFil: Ahmed, Asif. Aston University; Reino UnidoSchattauer Gmbh-Verlag Medizin Naturwissenschaften2015-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36887Ahmad, Shakil; Hewett, Peter W.; Fujisawa, Takeshi; Sissaoui, Samir; Cai, Meng; et al.; Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 113; 2; 2-2015; 329-3370340-6245CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1160/TH14-01-0002info:eu-repo/semantics/altIdentifier/url/https://th.schattauer.de/contents/archive/issue/2174/manuscript/23641.htmlinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:08:58Zoai:ri.conicet.gov.ar:11336/36887instacron: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:34982025-09-29 10:08:58.723CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
title Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
spellingShingle Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
Ahmad, Shakil
Angiogenesis
Carbon Monoxide
Endothelial Cells
Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-2
title_short Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
title_full Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
title_fullStr Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
title_full_unstemmed Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
title_sort Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
dc.creator.none.fl_str_mv Ahmad, Shakil
Hewett, Peter W.
Fujisawa, Takeshi
Sissaoui, Samir
Cai, Meng
Gueron, Geraldine
Al Ani, Bahjat
Cudmore, Melissa
Faraz Ahmed, S.
Wong, Michael K. K.
Wegiel, Barbara
Otterbein, Leo E.
Vítek, Libor
Ramma, Wenda
Wang, Keqing
Ahmed, Asif
author Ahmad, Shakil
author_facet Ahmad, Shakil
Hewett, Peter W.
Fujisawa, Takeshi
Sissaoui, Samir
Cai, Meng
Gueron, Geraldine
Al Ani, Bahjat
Cudmore, Melissa
Faraz Ahmed, S.
Wong, Michael K. K.
Wegiel, Barbara
Otterbein, Leo E.
Vítek, Libor
Ramma, Wenda
Wang, Keqing
Ahmed, Asif
author_role author
author2 Hewett, Peter W.
Fujisawa, Takeshi
Sissaoui, Samir
Cai, Meng
Gueron, Geraldine
Al Ani, Bahjat
Cudmore, Melissa
Faraz Ahmed, S.
Wong, Michael K. K.
Wegiel, Barbara
Otterbein, Leo E.
Vítek, Libor
Ramma, Wenda
Wang, Keqing
Ahmed, Asif
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiogenesis
Carbon Monoxide
Endothelial Cells
Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-2
topic Angiogenesis
Carbon Monoxide
Endothelial Cells
Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-2
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.
Fil: Ahmad, Shakil. Aston University; Reino Unido
Fil: Hewett, Peter W.. University Of Birmingham; Reino Unido
Fil: Fujisawa, Takeshi. University Of Birmingham; Reino Unido
Fil: Sissaoui, Samir. University Of Birmingham; Reino Unido
Fil: Cai, Meng. Aston University; Reino Unido
Fil: Gueron, Geraldine. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Al Ani, Bahjat. University Of Birmingham; Reino Unido
Fil: Cudmore, Melissa. University Of Birmingham; Reino Unido
Fil: Faraz Ahmed, S.. University of Liverpool; Reino Unido
Fil: Wong, Michael K. K.. University Of Southern California; Estados Unidos
Fil: Wegiel, Barbara. Harvard Medical School; Estados Unidos
Fil: Otterbein, Leo E.. Aston University; Reino Unido. Harvard Medical School; Estados Unidos
Fil: Vítek, Libor. Charles University; República Checa
Fil: Ramma, Wenda. Harvard Medical School; Estados Unidos
Fil: Wang, Keqing. Aston University; Reino Unido
Fil: Ahmed, Asif. Aston University; Reino Unido
description Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.
publishDate 2015
dc.date.none.fl_str_mv 2015-02
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/11336/36887
Ahmad, Shakil; Hewett, Peter W.; Fujisawa, Takeshi; Sissaoui, Samir; Cai, Meng; et al.; Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 113; 2; 2-2015; 329-337
0340-6245
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36887
identifier_str_mv Ahmad, Shakil; Hewett, Peter W.; Fujisawa, Takeshi; Sissaoui, Samir; Cai, Meng; et al.; Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 113; 2; 2-2015; 329-337
0340-6245
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1160/TH14-01-0002
info:eu-repo/semantics/altIdentifier/url/https://th.schattauer.de/contents/archive/issue/2174/manuscript/23641.html
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
dc.publisher.none.fl_str_mv Schattauer Gmbh-Verlag Medizin Naturwissenschaften
publisher.none.fl_str_mv Schattauer Gmbh-Verlag Medizin Naturwissenschaften
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 13.069144

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