Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy

Abstract The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor a...

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Autores principales:	Larissa B. Teixeira, Lucas T. Parreiras-e-Silva, Thiago Bruder-Nascimento, Diego A. Duarte, Sarah C. Simões, Rafael M. Costa, Deisy Y. Rodríguez, Pedro A. B. Ferreira, Carlos A. A. Silva, Emiliana P. Abrao, Eduardo B. Oliveira, Michel Bouvier, Rita C. Tostes, Claudio M. Costa-Neto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fef525bd7c04daf974776365ec10caf
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spelling	oai:doaj.org-article:2fef525bd7c04daf974776365ec10caf2021-12-02T15:05:19ZAng-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy10.1038/s41598-017-12074-32045-2322https://doaj.org/article/2fef525bd7c04daf974776365ec10caf2017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-12074-3https://doaj.org/toc/2045-2322Abstract The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R. Here we show that Ang-(1-7) binds to the AT1R without activating Gq, but triggering β-arrestins 1 and 2 recruitment and activation. Using an in vivo model of cardiac hypertrophy, we show that Ang-(1-7) significantly attenuates heart hypertrophy by reducing both heart weight and ventricular wall thickness and the increased end-diastolic pressure. Whereas neither the single blockade of AT1 or Mas receptors with their respective antagonists prevented the cardioprotective action of Ang1-7, combination of the two antagonists partially impaired the effect of Ang-(1-7). Taken together, these data indicate that Ang-(1-7) mediates at least part of its cardioprotective effects by acting as an endogenous β-arrestin-biased agonist at the AT1R.Larissa B. TeixeiraLucas T. Parreiras-e-SilvaThiago Bruder-NascimentoDiego A. DuarteSarah C. SimõesRafael M. CostaDeisy Y. RodríguezPedro A. B. FerreiraCarlos A. A. SilvaEmiliana P. AbraoEduardo B. OliveiraMichel BouvierRita C. TostesClaudio M. Costa-NetoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Larissa B. Teixeira Lucas T. Parreiras-e-Silva Thiago Bruder-Nascimento Diego A. Duarte Sarah C. Simões Rafael M. Costa Deisy Y. Rodríguez Pedro A. B. Ferreira Carlos A. A. Silva Emiliana P. Abrao Eduardo B. Oliveira Michel Bouvier Rita C. Tostes Claudio M. Costa-Neto Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
description	Abstract The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R. Here we show that Ang-(1-7) binds to the AT1R without activating Gq, but triggering β-arrestins 1 and 2 recruitment and activation. Using an in vivo model of cardiac hypertrophy, we show that Ang-(1-7) significantly attenuates heart hypertrophy by reducing both heart weight and ventricular wall thickness and the increased end-diastolic pressure. Whereas neither the single blockade of AT1 or Mas receptors with their respective antagonists prevented the cardioprotective action of Ang1-7, combination of the two antagonists partially impaired the effect of Ang-(1-7). Taken together, these data indicate that Ang-(1-7) mediates at least part of its cardioprotective effects by acting as an endogenous β-arrestin-biased agonist at the AT1R.
format	article
author	Larissa B. Teixeira Lucas T. Parreiras-e-Silva Thiago Bruder-Nascimento Diego A. Duarte Sarah C. Simões Rafael M. Costa Deisy Y. Rodríguez Pedro A. B. Ferreira Carlos A. A. Silva Emiliana P. Abrao Eduardo B. Oliveira Michel Bouvier Rita C. Tostes Claudio M. Costa-Neto
author_facet	Larissa B. Teixeira Lucas T. Parreiras-e-Silva Thiago Bruder-Nascimento Diego A. Duarte Sarah C. Simões Rafael M. Costa Deisy Y. Rodríguez Pedro A. B. Ferreira Carlos A. A. Silva Emiliana P. Abrao Eduardo B. Oliveira Michel Bouvier Rita C. Tostes Claudio M. Costa-Neto
author_sort	Larissa B. Teixeira
title	Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
title_short	Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
title_full	Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
title_fullStr	Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
title_full_unstemmed	Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
title_sort	ang-(1-7) is an endogenous β-arrestin-biased agonist of the at1 receptor with protective action in cardiac hypertrophy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2fef525bd7c04daf974776365ec10caf
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Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy

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