The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation
Autor (es)
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. ConcepciónEntidad
UAM. Departamento de Bioquímica; UAM. Departamento de Farmacología; UAM. Departamento de Obstetricia y Ginecología; Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Editor
Anatomical Society and John Wiley & Sons Ltd.Fecha de edición
2019-06-01Cita
10.1111/acel.12913
Aging Cell 18.3 (2019): :e12913.
ISSN
1474-9718 (print); 1474-9726 (online)DOI
10.1111/acel.12913Financiado por
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 PI17/01401Proyecto
Gobierno de España. SAF2017-84776-R; Gobierno de España. SAF2017-89714-R; Gobierno de España. PI17/01700; Gobierno de España. PI17/01401Versión del editor
https://doi.org/10.1111/acel.12913Materias
Angiotensin-(1-7); Endothelial senescence; Heme oxygenase-1; Klotho; Nuclear factor (erythroid-derived 2)-like 2; Vascular aging; FarmaciaDerechos
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley&Sons Ltd.Resumen
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.
Lista de ficheros
Google Scholar:Romero, Alejandra
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San Hipólito-Luengo, Álvaro
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Villalobos, Laura A.
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Vallejo, Susana
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Valencia, Inés
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Michalska, Patrycja
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Pajuelo-Lozano, Natalia
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Sánchez Pérez, María Isabel
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León, Rafael
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Bartha Rasero, José Luis
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Sanz, María Jesús
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Erusalimsky, Jorge D.
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Sánchez Ferrer, Carlos Félix
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Romacho, Tania
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Peiró Vallejo, M. Concepción
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