Angiotensin-(1-7) prevents T3-induced cardiomyocyte hypertrophy by upregulating FOXO3/SOD1/catalase and downregulating NF-x138;B

Autor(es)

Senger, Nathalia ^[1] ; C. Parletta, Aline ^[1] ; Marques, Bruno V. D. ^[2] ; Akamine, Eliana H. ^[2] ; Diniz, Gabriela P. ^[1] ; Campagnole-Santos, Maria J. ^[3] ; Santos, Robson A. S. ^[3] ; Barreto-Chaves, Maria Luiza M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 236, n. 4, p. 3059-3072, APR 2021.
• Citações Web of Science: 1

Resumo

Clinical studies have shown a correlation between thyroid disorders and cardiac diseases. High levels of triiodothyronine (T3) induce cardiac hypertrophy, a risk factor for cardiac complications and heart failure. Previous results have demonstrated that angiotensin-(1-7) is able to block T3-induced cardiac hypertrophy; however, the molecular mechanisms involved in this event have not been fully elucidated. Here, we evidenced the contribution of FOXO3 signaling to angiotensin-(1-7) effects. Angiotensin-(1-7) treatment increased nuclear FOXO3 levels and reduced p-FOXO3 levels (inactive form) in isolated cardiomyocytes. Knockdown of FOXO3 by RNA silencing abrogated the antihypertrophic effect of angiotensin-(1-7). Increased expression of antioxidant enzymes superoxide dismutase 1 (SOD1 and catalase) and lower levels of reactive oxygen species and nuclear factor-kappa B (NF-kappa B) were observed after angiotensin-(1-7) treatment in vitro. Consistent with these results, transgenic rats overexpressing angiotensin-(1-7) displayed increased nuclear FOXO3 and SOD1 levels and reduced NF-kappa B levels in the heart. These results provide a new molecular mechanism responsible for the antihypertrophic effect of angiotensin-(1-7), which may contribute to future therapeutic targets. (AU)

• Processo FAPESP: 16/13896-0 - Internalização do receptor de Ang II (AT1R) e ativação da sinalização Ras/Raf/MEK/ERK no estabelecimento da hipertrofia cardiomiocítica induzida por hormônios tiroideanos - envolvimento das beta-arrestinas
• Beneficiário: Maria Luiza de Morais Barreto de Chaves
• Modalidade de apoio: Auxílio à Pesquisa - Regular