Portal de investigación
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation
Fecha de publicación:
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Autores de INCLIVA
Participantes ajenos a INCLIVA
- Romero A
- San Hipólito-Luengo Á
- Villalobos LA
- Vallejo S
- Valencia I
- Michalska P
- Pajuelo-Lozano N
- Sánchez-Pérez I
- León R
- Bartha JL
- Erusalimsky JD
- Sánchez-Ferrer CF
- Romacho T
- Peiró C
Grupos y Plataformas de I+D+i
Abstract
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.
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd
Datos de la publicación
- ISSN/ISSNe:
- 1474-9718, 1474-9726
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.1111/acel.12913
- PubMed:
- 30773786
AGING CELL WILEY
Citas Recibidas en Web of Science: 94
Documentos
Filiaciones
Keywords
- angiotensin-(1-7); endothelial senescence; heme oxygenase-1; klotho; nuclear factor (erythroid-derived 2)-like 2; vascular aging
Proyectos y Estudios Clínicos
RETOS 2017. MODULACION FARMACOLOGICA DEL SISTEMA INMUNE COMO DIANA CLAVE EN LA PREVENCION DE LA ENFERMEDAD CARDIOVASCULAR ASOCIADA A DESORDENES METABOLICOS. SINTESIS DE FARMACOS NOVEDOSOS
Investigador Principal: MARIA JESUS SANZ FERRANDO
SAF2017-89714-R . MINISTERIO ECONOMIA Y COMPETITIVIDAD . 2018
Cita
Romero A,San Hipólito Á,Villalobos LA,Vallejo S,Valencia I,Michalska P,Pajuelo N,Sánchez I,León R,Bartha JL,Sanz MJ,Erusalimsky JD,Sánchez CF,Romacho T,Peiró C. The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation. Aging Cell. 2019. 18. (3):UNSP e12913. IF:7,238. (1).
The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation. Romero A, San Hipólito Á, Villalobos LA, Vallejo S, Valencia I, Michalska P, Pajuelo N et al. AGING CELL. 2019 junio 01. 18 (3):DOI:10.1111/acel.12913. PMID:30773786.
