Patients with hyperthyroidism exhibit increased risk of development and progression of cardiac diseases. The activation of the renin–angiotensin system (RAS) has been indirectly implicated in these cardiac effects observed in hyperthyroidism. Angiotensin-(1–7) (Ang-(1–7)) has previously been shown to counterbalance pathological effects of angiotensin II (Ang II). The aim of the present study was to investigate the effects of elevated circulating Ang-(1–7) levels on cardiac effects promoted by hyperthyroidism in a transgenic rat (TG) model that constitutively overexpresses an Ang-(1–7)-producing fusion protein [TGR(A1-7)3292]. TG and wild-type (WT) rats received daily injections (i.p.) of triiodothyronine (T3; 7 µg/100 g of body weight (BW)) or vehicle for 14 days. In contrast with WT rats, the TG rats did not develop cardiac hypertrophy after T3 treatment. Indeed, TG rats displayed reduced systolic blood pressure (SBP) and cardiac hyperdynamic condition induced by hyperthyroidism. Moreover, increased plasma levels of Ang II observed in hyperthyroid WT rats were prevented in TG rats. TG rats were protected from glycogen synthase kinase 3β (GSK3β) inactivation and nuclear factor of activated T cells (NFAT) nuclear accumulation induced by T3. In vitro studies evidenced that Ang-(1–7) prevented cardiomyocyte hypertrophy and GSK3β inactivation induced by T3. Taken together, these data reveal an important cardioprotective action of Ang-(1–7) in experimental model of hyperthyroidism.
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Double immunofluorescence staining for mindin (red) and CD68 (green) in atherosclerotic plaques of HFD-treated APOE-/- mice. In Issue 11 of Clinical Science, Zhu et al. discuss mindin deficiency as a novel mediator in protecting against foam cell formation and atherosclerosis, through direct interaction with LXR-β; for details, see pages 1199–1213.
Research Article|
June 05 2018
Angiotensin-(1–7) reduces cardiac effects of thyroid hormone by GSK3Β/NFATc3 signaling pathway
Nathalia Senger;
Nathalia Senger
1Department of Anatomy, University of São Paulo, São Paulo, Brazil
3Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Brazil
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Marcos Barrouin Melo;
Marcos Barrouin Melo
2Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
3Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Brazil
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Gabriela Placoná Diniz;
Gabriela Placoná Diniz
1Department of Anatomy, University of São Paulo, São Paulo, Brazil
3Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Brazil
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Maria José Campagnole-Santos;
Maria José Campagnole-Santos
2Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
3Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Brazil
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Robson Augusto Souza Santos;
Robson Augusto Souza Santos
2Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
3Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Brazil
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Maria Luiza M. Barreto-Chaves
1Department of Anatomy, University of São Paulo, São Paulo, Brazil
3Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Brazil
Correspondence: Maria Luiza M. Barreto-Chaves ([email protected])
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Publisher: Portland Press Ltd
Received:
December 08 2017
Revision Received:
April 12 2018
Accepted:
April 23 2018
Accepted Manuscript online:
April 23 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (11): 1117–1133.
Article history
Received:
December 08 2017
Revision Received:
April 12 2018
Accepted:
April 23 2018
Accepted Manuscript online:
April 23 2018
Citation
Nathalia Senger, Marcos Barrouin Melo, Gabriela Placoná Diniz, Maria José Campagnole-Santos, Robson Augusto Souza Santos, Maria Luiza M. Barreto-Chaves; Angiotensin-(1–7) reduces cardiac effects of thyroid hormone by GSK3Β/NFATc3 signaling pathway. Clin Sci (Lond) 14 June 2018; 132 (11): 1117–1133. doi: https://doi.org/10.1042/CS20171606
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