Independent anti-angiogenic capacities of coagulation factors X and Xa

Autores
Lange, Soledad; Gonzalez, Ibeth; Pinto, Mauricio P.; Arce, Maximiliano; Valenzuela, Rodrigo; Aranda, Evelyn; Elliot, Matias; Alvarez, Marjorie; Henriquez, Soledad; Velazquez, Ethel; Orge, Felipe; Oliva, Bárbara; Gonzalez, Pamela; Villalon, Manuel; Cautivo, Kelly M.; Kalergis, Alexis M.; Pereira, Karla; Mendoza, Camila; Saez, Claudia; Kato, Sumie; Cuello, Mauricio; Parborell, Maria Fernanda Agustina; Irusta, Griselda; Palma, Verónica; Allende, Miguel L.; Owen, Gareth I.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Knockout models have shown that the coagulation system has a role in vascular development and angiogenesis. Herein, we report for the first time that zymogen FX and its active form (FXa) possess anti-angiogenic properties. Both the recombinant FX and FXa inhibit angiogenesis in vitro using endothelial EA.hy926 and human umbilical cord vascular endothelial cells (HUVEC). This effect is dependent on the Gla domain of FX. We demonstrate that FX and FXa use different mechanisms: the use of Rivaroxaban (RX) a specific inhibitor of FXa attenuated its anti-angiogenic properties but did not modify the anti-angiogenic effect of FX. Furthermore, only the anti-angiogenic activity of FXa is PAR-1dependent. Using in vivo models, we show that FX and FXa are anti-angiogenic in the zebrafish intersegmental vasculature (ISV) formation and in the chick embryo chorioallantoic membrane (CAM) assays. Our results provide further evidence for the non-hemostatic functions of FX and FXa and demonstrate for the first time a biological role for the zymogen FX.
Fil: Lange, Soledad. Pontificia Universidad Católica de Chile; Chile
Fil: Gonzalez, Ibeth. Pontificia Universidad Católica de Chile; Chile
Fil: Pinto, Mauricio P.. Pontificia Universidad Católica de Chile; Chile
Fil: Arce, Maximiliano. Pontificia Universidad Católica de Chile; Chile
Fil: Valenzuela, Rodrigo. Pontificia Universidad Católica de Chile; Chile
Fil: Aranda, Evelyn. Pontificia Universidad Católica de Chile; Chile
Fil: Elliot, Matias. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Alvarez, Marjorie. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Henriquez, Soledad. Pontificia Universidad Católica de Chile; Chile
Fil: Velazquez, Ethel. Pontificia Universidad Católica de Chile; Chile
Fil: Orge, Felipe. Pontificia Universidad Católica de Chile; Chile
Fil: Oliva, Bárbara. Pontificia Universidad Católica de Chile; Chile
Fil: Gonzalez, Pamela. Pontificia Universidad Católica de Chile; Chile
Fil: Villalon, Manuel. Pontificia Universidad Católica de Chile; Chile
Fil: Cautivo, Kelly M.. Pontificia Universidad Católica de Chile; Chile
Fil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; Chile
Fil: Pereira, Karla. Pontificia Universidad Católica de Chile; Chile
Fil: Mendoza, Camila. Pontificia Universidad Católica de Chile; Chile
Fil: Saez, Claudia. Pontificia Universidad Católica de Chile; Chile
Fil: Kato, Sumie. Pontificia Universidad Católica de Chile; Chile
Fil: Cuello, Mauricio. Pontificia Universidad Católica de Chile; Chile
Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Palma, Verónica. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Allende, Miguel L.. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Owen, Gareth I.. Pontificia Universidad Católica de Chile; Chile. Biomedical Research Consortium Chile; Chile
Materia
Angiogenesis Inhibitors
Coagulation
Fx
Fxa
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:11336/6443

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spelling Independent anti-angiogenic capacities of coagulation factors X and XaLange, SoledadGonzalez, IbethPinto, Mauricio P.Arce, MaximilianoValenzuela, RodrigoAranda, EvelynElliot, MatiasAlvarez, MarjorieHenriquez, SoledadVelazquez, EthelOrge, FelipeOliva, BárbaraGonzalez, PamelaVillalon, ManuelCautivo, Kelly M.Kalergis, Alexis M.Pereira, KarlaMendoza, CamilaSaez, ClaudiaKato, SumieCuello, MauricioParborell, Maria Fernanda AgustinaIrusta, GriseldaPalma, VerónicaAllende, Miguel L.Owen, Gareth I.Angiogenesis InhibitorsCoagulationFxFxahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Knockout models have shown that the coagulation system has a role in vascular development and angiogenesis. Herein, we report for the first time that zymogen FX and its active form (FXa) possess anti-angiogenic properties. Both the recombinant FX and FXa inhibit angiogenesis in vitro using endothelial EA.hy926 and human umbilical cord vascular endothelial cells (HUVEC). This effect is dependent on the Gla domain of FX. We demonstrate that FX and FXa use different mechanisms: the use of Rivaroxaban (RX) a specific inhibitor of FXa attenuated its anti-angiogenic properties but did not modify the anti-angiogenic effect of FX. Furthermore, only the anti-angiogenic activity of FXa is PAR-1dependent. Using in vivo models, we show that FX and FXa are anti-angiogenic in the zebrafish intersegmental vasculature (ISV) formation and in the chick embryo chorioallantoic membrane (CAM) assays. Our results provide further evidence for the non-hemostatic functions of FX and FXa and demonstrate for the first time a biological role for the zymogen FX.Fil: Lange, Soledad. Pontificia Universidad Católica de Chile; ChileFil: Gonzalez, Ibeth. Pontificia Universidad Católica de Chile; ChileFil: Pinto, Mauricio P.. Pontificia Universidad Católica de Chile; ChileFil: Arce, Maximiliano. Pontificia Universidad Católica de Chile; ChileFil: Valenzuela, Rodrigo. Pontificia Universidad Católica de Chile; ChileFil: Aranda, Evelyn. Pontificia Universidad Católica de Chile; ChileFil: Elliot, Matias. Universidad de Chile. Facultad de Ciencias; ChileFil: Alvarez, Marjorie. Universidad de Chile. Facultad de Ciencias; ChileFil: Henriquez, Soledad. Pontificia Universidad Católica de Chile; ChileFil: Velazquez, Ethel. Pontificia Universidad Católica de Chile; ChileFil: Orge, Felipe. Pontificia Universidad Católica de Chile; ChileFil: Oliva, Bárbara. Pontificia Universidad Católica de Chile; ChileFil: Gonzalez, Pamela. Pontificia Universidad Católica de Chile; ChileFil: Villalon, Manuel. Pontificia Universidad Católica de Chile; ChileFil: Cautivo, Kelly M.. Pontificia Universidad Católica de Chile; ChileFil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; ChileFil: Pereira, Karla. Pontificia Universidad Católica de Chile; ChileFil: Mendoza, Camila. Pontificia Universidad Católica de Chile; ChileFil: Saez, Claudia. Pontificia Universidad Católica de Chile; ChileFil: Kato, Sumie. Pontificia Universidad Católica de Chile; ChileFil: Cuello, Mauricio. Pontificia Universidad Católica de Chile; ChileFil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Palma, Verónica. Universidad de Chile. Facultad de Ciencias; ChileFil: Allende, Miguel L.. Universidad de Chile. Facultad de Ciencias; ChileFil: Owen, Gareth I.. Pontificia Universidad Católica de Chile; Chile. Biomedical Research Consortium Chile; ChileWiley2014-07-29info: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/11336/6443Lange, Soledad; Gonzalez, Ibeth; Pinto, Mauricio P.; Arce, Maximiliano; Valenzuela, Rodrigo; et al.; Independent anti-angiogenic capacities of coagulation factors X and Xa; Wiley; Journal of Cellular Physiology; 229; 11; 29-7-2014; 1673-16800021-95411097-4652enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24612info:eu-repo/semantics/altIdentifier/pmid/24615682info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24612/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:17Zoai:ri.conicet.gov.ar:11336/6443instacron: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 10:15:17.599CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Independent anti-angiogenic capacities of coagulation factors X and Xa
title Independent anti-angiogenic capacities of coagulation factors X and Xa
spellingShingle Independent anti-angiogenic capacities of coagulation factors X and Xa
Lange, Soledad
Angiogenesis Inhibitors
Coagulation
Fx
Fxa
title_short Independent anti-angiogenic capacities of coagulation factors X and Xa
title_full Independent anti-angiogenic capacities of coagulation factors X and Xa
title_fullStr Independent anti-angiogenic capacities of coagulation factors X and Xa
title_full_unstemmed Independent anti-angiogenic capacities of coagulation factors X and Xa
title_sort Independent anti-angiogenic capacities of coagulation factors X and Xa
dc.creator.none.fl_str_mv Lange, Soledad
Gonzalez, Ibeth
Pinto, Mauricio P.
Arce, Maximiliano
Valenzuela, Rodrigo
Aranda, Evelyn
Elliot, Matias
Alvarez, Marjorie
Henriquez, Soledad
Velazquez, Ethel
Orge, Felipe
Oliva, Bárbara
Gonzalez, Pamela
Villalon, Manuel
Cautivo, Kelly M.
Kalergis, Alexis M.
Pereira, Karla
Mendoza, Camila
Saez, Claudia
Kato, Sumie
Cuello, Mauricio
Parborell, Maria Fernanda Agustina
Irusta, Griselda
Palma, Verónica
Allende, Miguel L.
Owen, Gareth I.
author Lange, Soledad
author_facet Lange, Soledad
Gonzalez, Ibeth
Pinto, Mauricio P.
Arce, Maximiliano
Valenzuela, Rodrigo
Aranda, Evelyn
Elliot, Matias
Alvarez, Marjorie
Henriquez, Soledad
Velazquez, Ethel
Orge, Felipe
Oliva, Bárbara
Gonzalez, Pamela
Villalon, Manuel
Cautivo, Kelly M.
Kalergis, Alexis M.
Pereira, Karla
Mendoza, Camila
Saez, Claudia
Kato, Sumie
Cuello, Mauricio
Parborell, Maria Fernanda Agustina
Irusta, Griselda
Palma, Verónica
Allende, Miguel L.
Owen, Gareth I.
author_role author
author2 Gonzalez, Ibeth
Pinto, Mauricio P.
Arce, Maximiliano
Valenzuela, Rodrigo
Aranda, Evelyn
Elliot, Matias
Alvarez, Marjorie
Henriquez, Soledad
Velazquez, Ethel
Orge, Felipe
Oliva, Bárbara
Gonzalez, Pamela
Villalon, Manuel
Cautivo, Kelly M.
Kalergis, Alexis M.
Pereira, Karla
Mendoza, Camila
Saez, Claudia
Kato, Sumie
Cuello, Mauricio
Parborell, Maria Fernanda Agustina
Irusta, Griselda
Palma, Verónica
Allende, Miguel L.
Owen, Gareth I.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiogenesis Inhibitors
Coagulation
Fx
Fxa
topic Angiogenesis Inhibitors
Coagulation
Fx
Fxa
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Knockout models have shown that the coagulation system has a role in vascular development and angiogenesis. Herein, we report for the first time that zymogen FX and its active form (FXa) possess anti-angiogenic properties. Both the recombinant FX and FXa inhibit angiogenesis in vitro using endothelial EA.hy926 and human umbilical cord vascular endothelial cells (HUVEC). This effect is dependent on the Gla domain of FX. We demonstrate that FX and FXa use different mechanisms: the use of Rivaroxaban (RX) a specific inhibitor of FXa attenuated its anti-angiogenic properties but did not modify the anti-angiogenic effect of FX. Furthermore, only the anti-angiogenic activity of FXa is PAR-1dependent. Using in vivo models, we show that FX and FXa are anti-angiogenic in the zebrafish intersegmental vasculature (ISV) formation and in the chick embryo chorioallantoic membrane (CAM) assays. Our results provide further evidence for the non-hemostatic functions of FX and FXa and demonstrate for the first time a biological role for the zymogen FX.
Fil: Lange, Soledad. Pontificia Universidad Católica de Chile; Chile
Fil: Gonzalez, Ibeth. Pontificia Universidad Católica de Chile; Chile
Fil: Pinto, Mauricio P.. Pontificia Universidad Católica de Chile; Chile
Fil: Arce, Maximiliano. Pontificia Universidad Católica de Chile; Chile
Fil: Valenzuela, Rodrigo. Pontificia Universidad Católica de Chile; Chile
Fil: Aranda, Evelyn. Pontificia Universidad Católica de Chile; Chile
Fil: Elliot, Matias. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Alvarez, Marjorie. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Henriquez, Soledad. Pontificia Universidad Católica de Chile; Chile
Fil: Velazquez, Ethel. Pontificia Universidad Católica de Chile; Chile
Fil: Orge, Felipe. Pontificia Universidad Católica de Chile; Chile
Fil: Oliva, Bárbara. Pontificia Universidad Católica de Chile; Chile
Fil: Gonzalez, Pamela. Pontificia Universidad Católica de Chile; Chile
Fil: Villalon, Manuel. Pontificia Universidad Católica de Chile; Chile
Fil: Cautivo, Kelly M.. Pontificia Universidad Católica de Chile; Chile
Fil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; Chile
Fil: Pereira, Karla. Pontificia Universidad Católica de Chile; Chile
Fil: Mendoza, Camila. Pontificia Universidad Católica de Chile; Chile
Fil: Saez, Claudia. Pontificia Universidad Católica de Chile; Chile
Fil: Kato, Sumie. Pontificia Universidad Católica de Chile; Chile
Fil: Cuello, Mauricio. Pontificia Universidad Católica de Chile; Chile
Fil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Palma, Verónica. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Allende, Miguel L.. Universidad de Chile. Facultad de Ciencias; Chile
Fil: Owen, Gareth I.. Pontificia Universidad Católica de Chile; Chile. Biomedical Research Consortium Chile; Chile
description Knockout models have shown that the coagulation system has a role in vascular development and angiogenesis. Herein, we report for the first time that zymogen FX and its active form (FXa) possess anti-angiogenic properties. Both the recombinant FX and FXa inhibit angiogenesis in vitro using endothelial EA.hy926 and human umbilical cord vascular endothelial cells (HUVEC). This effect is dependent on the Gla domain of FX. We demonstrate that FX and FXa use different mechanisms: the use of Rivaroxaban (RX) a specific inhibitor of FXa attenuated its anti-angiogenic properties but did not modify the anti-angiogenic effect of FX. Furthermore, only the anti-angiogenic activity of FXa is PAR-1dependent. Using in vivo models, we show that FX and FXa are anti-angiogenic in the zebrafish intersegmental vasculature (ISV) formation and in the chick embryo chorioallantoic membrane (CAM) assays. Our results provide further evidence for the non-hemostatic functions of FX and FXa and demonstrate for the first time a biological role for the zymogen FX.
publishDate 2014
dc.date.none.fl_str_mv 2014-07-29
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/11336/6443
Lange, Soledad; Gonzalez, Ibeth; Pinto, Mauricio P.; Arce, Maximiliano; Valenzuela, Rodrigo; et al.; Independent anti-angiogenic capacities of coagulation factors X and Xa; Wiley; Journal of Cellular Physiology; 229; 11; 29-7-2014; 1673-1680
0021-9541
1097-4652
url http://hdl.handle.net/11336/6443
identifier_str_mv Lange, Soledad; Gonzalez, Ibeth; Pinto, Mauricio P.; Arce, Maximiliano; Valenzuela, Rodrigo; et al.; Independent anti-angiogenic capacities of coagulation factors X and Xa; Wiley; Journal of Cellular Physiology; 229; 11; 29-7-2014; 1673-1680
0021-9541
1097-4652
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24612
info:eu-repo/semantics/altIdentifier/pmid/24615682
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24612/abstract
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
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dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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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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