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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and involves nitric oxide production via Akt activation in mice

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Autor(es):
da Silva, Ivson Bezerra [1, 2] ; Gomes, Dayane Aparecida [3] ; Alenina, Natalia [4] ; Bader, Michael [4] ; dos Santos, Robson Augusto [5, 6, 7] ; Barreto-Chaves, Maria Luiza M. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Lab Cellular Biol & Funct Anat, Dept Anat, Inst Biomed Sci, Av Prof Lineu Prestes 2415, BR-05508900 Sao Paulo, SP - Brazil
[2] Univ Fed Paraiba, Dept Morphol, Hlth Sci Ctr, Human Anat, Joao Pessoa, Paraiba - Brazil
[3] Fed Univ Pernambuc, Dept Physiol, Biosci Ctr, Recife, PE - Brazil
[4] MaxDelbruck Ctr Mol Med, Berlin - Germany
[5] Univ Fed Minas Gerais, Natl Inst Sci & Technol Nanobiopharmaceut, Belo Horizonte, MG - Brazil
[6] Univ Fed Minas Gerais, Physiol & Biophys Dept, Belo Horizonte, MG - Brazil
[7] Fdn Cardiol, Cardiol Inst Rio Grande do Sul, Porto Alegre, RS - Brazil
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: HEART AND VESSELS; v. 33, n. 6, p. 671-681, JUN 2018.
Citações Web of Science: 2
Resumo

Studies have demonstrated that thyroid hormone (T3) can precondition the heart against ischaemic injury and improve post-ischaemic recovery. This study investigated whether the AT2 receptor (AT2R) is involved in cardioprotection and the potential molecular mechanism responsible for this effect. Hyperthyroidism was induced in male wild-type (WT) and AT2R knockout (KO) mice by administering daily intraperitoneal injections of T3 (7 mu g/100 g body weight) for 14 days. The mouse hearts were harvested and perfused with a Krebs-Henseleit solution at a constant flow in a Langendorff set-up. After 30 min of stabilization, the hearts were subjected to global ischaemia for 20 min and reperfused for 45 min. Baseline cardiac function was assessed by measuring four parameters: LVDP (mmHg), heart rate (bpm), + dP/dt and - dP/dt (mmHg/s). After reperfusion, the total protein from cardiac ventricles was obtained, and the Akt signalling pathway and NO production were evaluated. Post-ischaemic functional recovery was significantly greater (p < 0.05) in the T3-treated WT mice compared to the control, demonstrating the cardioprotective effect of T3. This effect was abolished in T3-treated KO mice, demonstrating the physiological relevance of AT2R to the cardioprotective phenotype induced by T3. Akt activation, iNOS expression and NO production increased in cardiac tissue after T3 treatment in the WT animals, but no difference was observed after treatment in the KO mice. This study indicates that AT2R acts as a cardioprotector in the case of hyperthyroidism. Strategies targeting AT2R agonists might improve cardiac function through NO production and suggest potential therapeutic targets for heart diseases. (AU)

Processo FAPESP: 13/04703-6 - Sistema renina angiotensina subcelular como possível mediador do efeito cardioprotetor do hormônio tireoidiano no modelo de isquemia/reperfusão
Beneficiário:Ivson Bezerra da Silva
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 11/12893-4 - Papel do receptor de Angiotensina II do tipo 2 (AT2) no efeito cardioprotetor do hormônio tiroideano, em modelo de isquemia/reperfusão
Beneficiário:Ivson Bezerra da Silva
Linha de fomento: Bolsas no Brasil - Mestrado