Angiotensin-(1–7) reduces cardiac effects of thyroid hormone by GSK3Β/NFATc3 signaling pathway

Abstract

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. 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.

Beta‐arrestin 2 mediates cardiac hypertrophy induced by thyroid hormones via AT1R

“…Sadoshima and colleagues showed the presence of intracellular vesicles in cardiomyocytes containing AngII that could be secreted under mechanical stretch (Sadoshima et al, 1993). Previous data of our group reported the increased expression of AngI/II in cardiac cells treated by TH-in vivo and in vitro-and the increased concentration of this peptide in the culture medium of cardiomyocytes (Diniz et al, 2009;Senger et al, 2018). However,…”

Impact of hyperthyroidism on cardiac hypertrophy

“…In the hyperthyroid state, an upregulation of Ang-(1-7), ACE2 activity and the MAS receptor in the heart was demonstrated, with no changes in the plasma levels of Ang-(1-7) (123). Contributing to these data, recently it was shown that elevated circulating levels of Ang-(1-7) prevented T3-induced cardiac hypertrophy by attenuating the glycogen synthase kinase 3 beta/nuclear factor of activated T-cells (GSK3β/NFATc3) signaling pathway (124) (Fig. 2).…”

Alterations in Expression of Neurodegeneration-Related Genes After Long-Term Potentiation in the Hippocampus of Hyperthyroid Rats

“…Thyroid hormones cause the activation of intracellular PI3K-Akt/Gsk3β and Mapk signaling pathways by interacting with the specialized membrane proteins monocarboxylate transporter 8 and integrin αVβ3, which are involved in the communication between the extracellular and intracellular environment, with their non-genomic effect. The non-genomic effects of thyroid hormones are short term [1][2][3][4] . The main effect of thyroid hormone is genomic, it binds to its receptors in the nucleus and initiates various transcription events and directly affects the biological functions of the cell 1 .…”