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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 \u03b2-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 \u03b2-arrestin-biased agonist of the AT1R. Here we show that Ang-(1-7) binds to the AT1R without activating Gq, but triggering \u03b2-arrestins 1 and 2 recruitment and activation. Using an\n                    <jats:italic>in vivo<\/jats:italic>\n                    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 AT\n                    <jats:sub>1<\/jats:sub>\n                    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 \u03b2-arrestin-biased agonist at the AT1R.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-12074-3","type":"journal-article","created":{"date-parts":[[2017,9,13]],"date-time":"2017-09-13T10:11:22Z","timestamp":1505297482000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Ang-(1-7) is an endogenous \u03b2-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy"],"prefix":"10.1038","volume":"7","author":[{"given":"Larissa B.","family":"Teixeira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas T.","family":"Parreiras-e-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"Bruder-Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Sim\u00f5es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael M.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deisy Y.","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A. 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