The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation
Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin–angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediati...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/688597 |
| Acceso en línea: | http://hdl.handle.net/10486/688597 https://dx.doi.org/10.1111/acel.12913 |
| Access Level: | acceso abierto |
| Palabra clave: | Angiotensin-(1-7) Endothelial senescence Heme oxygenase-1 Klotho Nuclear factor (erythroid-derived 2)-like 2 Vascular aging Farmacia |
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The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activationRomero, AlejandraSan Hipólito-Luengo, ÁlvaroVillalobos, Laura A.Vallejo, SusanaValencia, InésMichalska, PatrycjaPajuelo-Lozano, NataliaSánchez Pérez, María IsabelLeón, RafaelBartha Rasero, José LuisSanz, María JesúsErusalimsky, Jorge D.Sánchez Ferrer, Carlos FélixRomacho, TaniaPeiró Vallejo, M. ConcepciónAngiotensin-(1-7)Endothelial senescenceHeme oxygenase-1KlothoNuclear factor (erythroid-derived 2)-like 2Vascular agingFarmaciaEndothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin–angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. By activating the G protein-coupled receptor Mas, Ang-(1-7) inhibited the pro-senescence action of Ang II, but also of a non-RAS stressor such as the cytokine IL-1β. Moreover, Ang-(1-7) enhanced endothelial klotho levels, while klotho silencing resulted in the loss of the anti-senescence action of the heptapeptide. Indeed, both Ang-(1-7) and recombinant klotho activated the cytoprotective Nrf2/heme oxygenase-1 (HO-1) pathway. The HO-1 inhibitor tin protoporphyrin IX prevented the anti-senescence action evoked by Ang-(1-7) or recombinant klotho. Overall, the present study identifies Ang-(1-7) as an anti-senescence peptide displaying its protective action beyond the RAS by consecutively activating klotho and Nrf2/HO-1. Ang-(1-7) mimetic drugs may thus prove useful to prevent endothelial cell senescence and its related vascular complications.Plan Nacional I+D+i, Grant/Award Number: SAF2017-84776-R, SAF2017-89714-R; Fundación La Caixa, Grant/Award Number: CaixaImpulse CI17/00048; IS Carlos III, Grant/Award Number: PI17/01700 and PI17/01401Anatomical Society and John Wiley & Sons Ltd.Departamento de FarmacologíaDepartamento de Obstetricia y GinecologíaDepartamento de BioquímicaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)20192019-06-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/688597https://dx.doi.org/10.1111/acel.12913reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6885972026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| title |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| spellingShingle |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation Romero, Alejandra Angiotensin-(1-7) Endothelial senescence Heme oxygenase-1 Klotho Nuclear factor (erythroid-derived 2)-like 2 Vascular aging Farmacia |
| title_short |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| title_full |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| title_fullStr |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| title_full_unstemmed |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| title_sort |
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation |
| dc.creator.none.fl_str_mv |
Romero, Alejandra San Hipólito-Luengo, Álvaro Villalobos, Laura A. Vallejo, Susana Valencia, Inés Michalska, Patrycja Pajuelo-Lozano, Natalia Sánchez Pérez, María Isabel León, Rafael Bartha Rasero, José Luis Sanz, María Jesús Erusalimsky, Jorge D. Sánchez Ferrer, Carlos Félix Romacho, Tania Peiró Vallejo, M. Concepción |
| author |
Romero, Alejandra |
| author_facet |
Romero, Alejandra San Hipólito-Luengo, Álvaro Villalobos, Laura A. Vallejo, Susana Valencia, Inés Michalska, Patrycja Pajuelo-Lozano, Natalia Sánchez Pérez, María Isabel León, Rafael Bartha Rasero, José Luis Sanz, María Jesús Erusalimsky, Jorge D. Sánchez Ferrer, Carlos Félix Romacho, Tania Peiró Vallejo, M. Concepción |
| author_role |
author |
| author2 |
San Hipólito-Luengo, Álvaro Villalobos, Laura A. Vallejo, Susana Valencia, Inés Michalska, Patrycja Pajuelo-Lozano, Natalia Sánchez Pérez, María Isabel León, Rafael Bartha Rasero, José Luis Sanz, María Jesús Erusalimsky, Jorge D. Sánchez Ferrer, Carlos Félix Romacho, Tania Peiró Vallejo, M. Concepción |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Farmacología Departamento de Obstetricia y Ginecología Departamento de Bioquímica Facultad de Medicina Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) |
| dc.subject.none.fl_str_mv |
Angiotensin-(1-7) Endothelial senescence Heme oxygenase-1 Klotho Nuclear factor (erythroid-derived 2)-like 2 Vascular aging Farmacia |
| topic |
Angiotensin-(1-7) Endothelial senescence Heme oxygenase-1 Klotho Nuclear factor (erythroid-derived 2)-like 2 Vascular aging Farmacia |
| description |
Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin–angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. By activating the G protein-coupled receptor Mas, Ang-(1-7) inhibited the pro-senescence action of Ang II, but also of a non-RAS stressor such as the cytokine IL-1β. Moreover, Ang-(1-7) enhanced endothelial klotho levels, while klotho silencing resulted in the loss of the anti-senescence action of the heptapeptide. Indeed, both Ang-(1-7) and recombinant klotho activated the cytoprotective Nrf2/heme oxygenase-1 (HO-1) pathway. The HO-1 inhibitor tin protoporphyrin IX prevented the anti-senescence action evoked by Ang-(1-7) or recombinant klotho. Overall, the present study identifies Ang-(1-7) as an anti-senescence peptide displaying its protective action beyond the RAS by consecutively activating klotho and Nrf2/HO-1. Ang-(1-7) mimetic drugs may thus prove useful to prevent endothelial cell senescence and its related vascular complications. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-06-01 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 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 |
http://hdl.handle.net/10486/688597 https://dx.doi.org/10.1111/acel.12913 |
| url |
http://hdl.handle.net/10486/688597 https://dx.doi.org/10.1111/acel.12913 |
| 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 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Anatomical Society and John Wiley & Sons Ltd. |
| publisher.none.fl_str_mv |
Anatomical Society and John Wiley & Sons Ltd. |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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15,300719 |