Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.

Hernández Navarro, Ignacio; Botana Veguillas, Laura; Diez Mata, Javier; Tesoro Santos, Laura; Jiménez Guirado, Beatriz; Gonzalez-Cucharero, Claudia; Alcharani, Nunzio; Zamorano, Jose Luis; Saura, Marta; Zaragoza; Zaragoza Sánchez, Carlos

Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.

Vascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelia...

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Detalles Bibliográficos
Autores:	Hernández Navarro, Ignacio, Botana Veguillas, Laura, Diez Mata, Javier, Tesoro Santos, Laura, Jiménez Guirado, Beatriz, Gonzalez-Cucharero, Claudia, Alcharani, Nunzio, Zamorano, Jose Luis, Saura, Marta, Zaragoza, Zaragoza Sánchez, Carlos
Tipo de recurso:	artículo
Fecha de publicación:	2024
País:	España
Institución:	Universidad Francisco de Vitoria
Repositorio:	DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:	inglés
OAI Identifier:	oai:ddfv.ufv.es:10641/5516
Acceso en línea:	https://hdl.handle.net/10641/5516
Access Level:	acceso abierto
Palabra clave:	Endothelial senescence Nitric oxide Endothelial nitric oxide synthase Uncoupling Tetrahydrobiopterin Oxidative stress Inflammation Cyclophilin A (CypA) Extracellular matrix metalloprotease inducer

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network_acronym_str	ES
network_name_str	España
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spelling	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.Hernández Navarro, IgnacioBotana Veguillas, LauraDiez Mata, JavierTesoro Santos, LauraJiménez Guirado, BeatrizGonzalez-Cucharero, ClaudiaAlcharani, NunzioZamorano, Jose LuisSaura, MartaZaragozaZaragoza Sánchez, CarlosEndothelial senescenceNitric oxideEndothelial nitric oxide synthaseUncouplingTetrahydrobiopterinOxidative stressInflammationCyclophilin A (CypA)Extracellular matrix metalloprotease inducerVascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelial cells undergo an irreversible growth arrest and alter their functional state after a finite number of divisions, a phenomenon called replicative senescence. We assessed the contribution of NO during replicative senescence of human aortic (HAEC) and coronary (CAEC) endothelial cells, in which accumulation of the senescence marker SA-β-Gal was quantified by β-galactosidase staining on cultured cells. We found a negative correlation in passaged cell cultures from P0 to P12, between a reduction in NO production with increased ES and the formation of reactive oxygen (ROS) and nitrogen (ONOO−) species, indicative of oxidative and nitrosative stress. The effect of ES was evidenced by reduced expression of endothelial Nitric Oxide Synthase (eNOS), Interleukin Linked Kinase (ILK), and Heat shock protein 90 (Hsp90), alongside a significant increase in the BH2/BH4 ratio, inducing the uncoupling of eNOS, favoring the production of superoxide and peroxynitrite species, and fostering an inflammatory environment, as confirmed by the levels of Cyclophilin A (CypA) and its receptor Extracellular Matrix Metalloprotease Inducer (EMMPRIN). NO prevents ES by preventing the uncoupling of eNOS, in which oxidation of BH4, which plays a key role in eNOS producing NO, may play a critical role in launching the release of free radical species, triggering an aging-related inflammatory response.MDPI20242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/5516reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/55162026-06-11T12:44:57Z
dc.title.none.fl_str_mv	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
title	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
spellingShingle	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS. Hernández Navarro, Ignacio Endothelial senescence Nitric oxide Endothelial nitric oxide synthase Uncoupling Tetrahydrobiopterin Oxidative stress Inflammation Cyclophilin A (CypA) Extracellular matrix metalloprotease inducer
title_short	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
title_full	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
title_fullStr	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
title_full_unstemmed	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
title_sort	Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.
dc.creator.none.fl_str_mv	Hernández Navarro, Ignacio Botana Veguillas, Laura Diez Mata, Javier Tesoro Santos, Laura Jiménez Guirado, Beatriz Gonzalez-Cucharero, Claudia Alcharani, Nunzio Zamorano, Jose Luis Saura, Marta Zaragoza Zaragoza Sánchez, Carlos
author	Hernández Navarro, Ignacio
author_facet	Hernández Navarro, Ignacio Botana Veguillas, Laura Diez Mata, Javier Tesoro Santos, Laura Jiménez Guirado, Beatriz Gonzalez-Cucharero, Claudia Alcharani, Nunzio Zamorano, Jose Luis Saura, Marta Zaragoza Zaragoza Sánchez, Carlos
author_role	author
author2	Botana Veguillas, Laura Diez Mata, Javier Tesoro Santos, Laura Jiménez Guirado, Beatriz Gonzalez-Cucharero, Claudia Alcharani, Nunzio Zamorano, Jose Luis Saura, Marta Zaragoza Zaragoza Sánchez, Carlos
author2_role	author author author author author author author author author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	Endothelial senescence Nitric oxide Endothelial nitric oxide synthase Uncoupling Tetrahydrobiopterin Oxidative stress Inflammation Cyclophilin A (CypA) Extracellular matrix metalloprotease inducer
topic	Endothelial senescence Nitric oxide Endothelial nitric oxide synthase Uncoupling Tetrahydrobiopterin Oxidative stress Inflammation Cyclophilin A (CypA) Extracellular matrix metalloprotease inducer
description	Vascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelial cells undergo an irreversible growth arrest and alter their functional state after a finite number of divisions, a phenomenon called replicative senescence. We assessed the contribution of NO during replicative senescence of human aortic (HAEC) and coronary (CAEC) endothelial cells, in which accumulation of the senescence marker SA-β-Gal was quantified by β-galactosidase staining on cultured cells. We found a negative correlation in passaged cell cultures from P0 to P12, between a reduction in NO production with increased ES and the formation of reactive oxygen (ROS) and nitrogen (ONOO−) species, indicative of oxidative and nitrosative stress. The effect of ES was evidenced by reduced expression of endothelial Nitric Oxide Synthase (eNOS), Interleukin Linked Kinase (ILK), and Heat shock protein 90 (Hsp90), alongside a significant increase in the BH2/BH4 ratio, inducing the uncoupling of eNOS, favoring the production of superoxide and peroxynitrite species, and fostering an inflammatory environment, as confirmed by the levels of Cyclophilin A (CypA) and its receptor Extracellular Matrix Metalloprotease Inducer (EMMPRIN). NO prevents ES by preventing the uncoupling of eNOS, in which oxidation of BH4, which plays a key role in eNOS producing NO, may play a critical role in launching the release of free radical species, triggering an aging-related inflammatory response.
publishDate	2024
dc.date.none.fl_str_mv	2024 2024-01-01 2024 2024-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10641/5516
url	https://hdl.handle.net/10641/5516
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	MDPI
publisher.none.fl_str_mv	MDPI
dc.source.none.fl_str_mv	reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria instname:Universidad Francisco de Vitoria
instname_str	Universidad Francisco de Vitoria
reponame_str	DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection	DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.812429

Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS.

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