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Subcellular renin angiotensin system as mediator of the cardioprotective effector of thyroid hormone in ischemia reperfusion model

Grant number: 13/04703-6
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2013
Effective date (End): May 15, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Maria Luiza de Morais Barreto de Chaves
Grantee:Ivson Bezerra da Silva
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):14/21464-8 - Does Caveolin-1 (Cav-1) modulate arrhythmogenecity by regulating cSrc tyrosine kinase and cardiac gap junction homeostasis? Role of thyroid hormone, BE.EP.DD

Abstract

The heart is subjected to different hormonal stimulus, which can directly or indirectly influence its trophic status. The angiotensin II (Ang II), characterized as the main effector of Renin-Angiotensin System (RAS), is a potent vasoactive peptide and exerts numerous biological effects through its receptors (AT1 and AT2). In cardiac tissue, Ang II promotes cardiomyocyte hypertrophy and hyperplasia of fibroblasts. The heart corresponds to the main target of thyroid hormones (TH), which also influence the cardiac trophism. In the last years we and other authors have shown a close relationship between TH-induced cardiac hypertrophy and RAS activation. Thus, hyperthyroid rats treated with AT1 receptor inhibitor (losartan) presented prevention of hypertrophy both in vivo and in vitro. On the other hand, the AT1 inhibition did not abolish the cardioprotective effect of TH on Ischemia/Reperfusion (I/R) experimental model. Considering that: the role of AT2 receptors is not well defined in adult animals that recent studies have shown that I/R promotes decrease on AT2 receptor expression in the myocardium and that in the hyperthyroidism condition the AT2 expression is increased (about 50%) in the heart, we have hypothesized that the cardioprotective effect of TH in I/R model may occur with the participation of AT2 receptor. This hypothesis is being tested using I/R experimental model in isolated hearts of AT2 knockout mice submitted to high levels of the T3 during reperfusion time. The role of nitric oxide synthases (NOS), also activated by high levels of TH, and normally triggered in response to ischemic stress and described as responsible for the increased synthesis of nitric oxide (NO) will be evaluated, and also the participation of SRA subcellular mitochondrial. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEDROSO, JOAO A. B.; DA SILVA, IVSON B.; ZAMPIERI, THAIS T.; TOTOLA, LEONARDO T.; MOREIRA, THIAGO S.; TANIGUTI, ANA P. T.; DINIZ, GABRIELA P.; BARRETO-CHAVES, MARIA LUIZA M.; DONATO, JOSE, JR.. SOCS3 Ablation in Leptin Receptor-Expressing Cells Causes Autonomic and Cardiac Dysfunctions in Middle-Aged Mice despite Improving Energy and Glucose Metabolism. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 12, p. 19-pg., . (12/15517-6, 11/12893-4, 10/18086-0, 13/04703-6, 13/25032-2)
DA SILVA, IVSON BEZERRA; GOMES, DAYANE APARECIDA; ALENINA, NATALIA; BADER, MICHAEL; DOS SANTOS, ROBSON AUGUSTO; BARRETO-CHAVES, MARIA LUIZA M.. Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and involves nitric oxide production via Akt activation in mice. HEART AND VESSELS, v. 33, n. 6, p. 671-681, . (11/12893-4, 13/04703-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Ivson Bezerra da. The cardioprotective effect of thyroid hormone in ischemia reperfusion experimental model: role of renin angiotensin system.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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