Angiotensin type 1 (AT1) and type 2 (AT2) receptors mediate the increase in TGF-β1 in thyroid hormone-induced cardiac hypertrophy

Increased thyroid hormone (TH) levels are known to induce cardiac hypertrophy. Some studies have provided evidence for a functional link between angiotensin II (ANG II) and transforming growth factor beta 1 (TGF-beta 1) in the heart, both being able to also induce cardiac hypertrophy. However, the contribution of this growth factor activated directly by TH or indirectly by ANG II in cardiac hypertrophy development remains unknown. To analyze the possible role of TGF-beta 1 in cardiac hypertrophy induced by TH and also to evaluate if the TGF-beta 1 effect is mediated by ANG II receptors, we employed Wistar rats separated into control, hypothyroid (hypo) and hyperthyroid (T4-10) groups combined or not with ANG II receptor blockers (losartan or PD123319). Serum levels of T3 and T4, systolic pressure and heart rate confirmed the thyroid state of the groups. The T4-10 group presented a significant increase in cardiac TGF-beta 1 levels; however, TGF-beta 1 levels in the hypo group did not change in relation to the control. Inhibition of the increase in cardiac TGF-beta 1 levels was observed in the groups treated with T4 in association with losartan or PD123319 when compared to the T4-10 group. These results demonstrate for the first time the TH-modulated induction of cardiac TGF-beta 1 in cardiac hypertrophy, and that this effect is mediated by ANG II receptors.