AT1 receptor knockdown prevents the T3‐induced cardiomyocyte hypertrophy: modulation of the Akt Signaling Pathway

Abstract

ObjectiveThe Renin Angiotensin System plays an important role in TH‐induced cardiac hypertrophy. We recently demonstrated the in vivo participation of Angiotensin II Type 1 receptor (AT1R) in TH‐induced cardiac hypertrophy. The aim of this study was to analyze the contribution of AT1R to the development of T3‐induced cardiomyocyte hypertrophy, as well as to evaluate the role that AT1R plays in the activation of the Akt/GSK‐3β/mTOR signaling pathway promoted by T3.MethodsCardiomyocytes cultures were prepared from ventricles of neonatal Wistar rats by colagenase/pancreatin method. The cells were transfected with a selective AT1R small interfering RNA (AT1R siRNA). The AT1R knockdown was evaluated by Real Time PCR and Western Blot. Protein synthesis was quantified by tritiated leucine incorporation. The Akt/GSK‐3β/mTOR signaling pathway was analyzed by Western Blot. The results were expressed as mean±SD and P0.05 (n=3).ResultsThe cells transfected with the AT1R siRNA presented reduced mRNA and protein expression of AT1R (P<0.01). AT1R knockdown prevented the T3‐induced cardiomyocyte hypertrophy, as evidenced by the reduction in protein synthesis (P<0.01). In addition, the AT1R siRNA diminished the T3‐induced activation of the Akt/GSK‐3β/mTOR (P<0.01). These data demonstrate for the first time that the AT1R contributes to the trophic effect that T3 has on cardiomyocytes, as well as in the nongenomic T3 effect on the Akt/GSK‐3β/mTOR signaling pathway in cardiomyocytes.Financial Support: FAPESP.