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...

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Autores: Romero A, San Hipólito-Luengo Á, Villalobos LA, Vallejo S, Valencia I, Michalska P, Pajuelo-Lozano N, Sánchez-Pérez I, León R, Bartha JL, Sanz MJ, Erusalimsky JD, Sánchez-Ferrer CF, Romacho T, Peiró C
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p2861
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/2861
Access Level:acceso abierto
Palabra clave:angiotensin-(1-7)
endothelial senescence
heme oxygenase-1
klotho
nuclear factor (erythroid-derived 2)-like 2
vascular aging
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spelling The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activationRomero ASan Hipólito-Luengo ÁVillalobos LAVallejo SValencia IMichalska PPajuelo-Lozano NSánchez-Pérez ILeón RBartha JLSanz MJErusalimsky JDSánchez-Ferrer CFRomacho TPeiró Cangiotensin-(1-7)endothelial senescenceheme oxygenase-1klothonuclear factor (erythroid-derived 2)-like 2vascular agingEndothelial 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-beta-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-1 beta. 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.WILEY2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/2861AGING CELLISSN: 14749718ISSNe: 14749726reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p28612026-06-07T16:35:31Z
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 A
angiotensin-(1-7)
endothelial senescence
heme oxygenase-1
klotho
nuclear factor (erythroid-derived 2)-like 2
vascular aging
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 A
San Hipólito-Luengo Á
Villalobos LA
Vallejo S
Valencia I
Michalska P
Pajuelo-Lozano N
Sánchez-Pérez I
León R
Bartha JL
Sanz MJ
Erusalimsky JD
Sánchez-Ferrer CF
Romacho T
Peiró C
author Romero A
author_facet Romero A
San Hipólito-Luengo Á
Villalobos LA
Vallejo S
Valencia I
Michalska P
Pajuelo-Lozano N
Sánchez-Pérez I
León R
Bartha JL
Sanz MJ
Erusalimsky JD
Sánchez-Ferrer CF
Romacho T
Peiró C
author_role author
author2 San Hipólito-Luengo Á
Villalobos LA
Vallejo S
Valencia I
Michalska P
Pajuelo-Lozano N
Sánchez-Pérez I
León R
Bartha JL
Sanz MJ
Erusalimsky JD
Sánchez-Ferrer CF
Romacho T
Peiró C
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv angiotensin-(1-7)
endothelial senescence
heme oxygenase-1
klotho
nuclear factor (erythroid-derived 2)-like 2
vascular aging
topic angiotensin-(1-7)
endothelial senescence
heme oxygenase-1
klotho
nuclear factor (erythroid-derived 2)-like 2
vascular aging
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-beta-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-1 beta. 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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/2861
url https://incliva.portalinvestigacion.com/publicaciones/2861
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv AGING CELL
ISSN: 14749718
ISSNe: 14749726
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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