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Beta\u2010arrestin (ARRB) signaling has been described as noncanonical signal transduction pathway that exerts important effects in the cardiovascular system through G\u2010protein\u2010coupled receptors, as AT1R. Herein, we investigated the contribution of ARRB signaling in TH\u2010induced cardiomyocyte hypertrophy. Primary cardiomyocyte\u00a0cultures were treated with Triiodothyronine (T3) to induce cell hypertrophy. T3 rapidly activates extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2) signaling, which was partially inhibited by AT1R blockade. Also, ERK1\/2 inhibition attenuated the hypertrophic effects of T3. ARRB2 was upregulated by T3, and small interfering RNA assays revealed the role of ARRB2\u2014but not ARRB1\u2014on ERK1\/2 activation and cardiomyocyte hypertrophy. Corroborating these findings, the ARRB2\u2010overexpressed cells showed increased expression of hypertrophic markers, which were attenuated by ERK1\/2 inhibition. Immunocytochemistry and immunoprecipitation assays revealed the increased expression of nuclear AT1R after T3 stimulation and the increased interaction of AT1R\/ARRB2. The inhibition of endocytosis also attenuated the T3 effects on cardiac cells. Our results evidence the contribution of ARRB2 on ERK1\/2 activation and cardiomyocyte hypertrophy induced by T3 via AT1R.<\/jats:p>","DOI":"10.1002\/jcp.30187","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T17:25:04Z","timestamp":1608571504000},"page":"4640-4654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Beta\u2010arrestin 2 mediates cardiac hypertrophy induced by thyroid hormones via AT1R"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7097-6960","authenticated-orcid":false,"given":"Caroline Antunes","family":"Lino","sequence":"first","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences University of Sao Paulo  Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4266-8872","authenticated-orcid":false,"given":"Larissa","family":"de Bortoli 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