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Doctoral Thesis
DOI
10.11606/T.42.2010.tde-25032010-143422
Document
Author
Full name
Gabriela Placoná Diniz
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Chaves, Maria Luiza Morais Barreto de (President)
Heimann, Joel Claudio
Klein, Adriane Belló
Nunes, Maria Tereza
Santos, Robson Augusto Souza dos
Title in Portuguese
Avaliação da contribuição do receptor AT1 de angiotensina II e do papel da via de sinalização AKT/GSK-3/mTOR no processo de hipertrofia do cardiomiócito induzido pelo hormônio tiroideano
Keywords in Portuguese
Cardiomiócitos
Hipertrofia cardíaca
Hormônios tiroideanos
Receptores de angiotensina
RNA de interferência
Sistema renina-angiotensina
Abstract in Portuguese
O presente estudo avaliou o papel do receptor AT1 de Angiotensina II no desenvolvimento da hipertrofia dos cardiomiócitos promovida pelo T3, bem como a participação dos mecanismos intracelulares deflagrados pelo receptor AT1 neste modelo de hipertrofia cardíaca. O silenciamento do receptor AT1 com RNA de interferência preveniu totalmente o desenvolvimento da hipertrofia dos cardiomiócitos induzida pelo T3. Os cardiomiócitos tratados com T3 demonstraram uma rápida ativação da via da Akt/GSK-3/mTOR, a qual foi atenuada ou prevenida pelo silenciamento do receptor AT1. Ainda, a expressão de Angiotensina I/II no lisado celular e a expressão do receptor AT1 foram rapidamente aumentados pelo T3. Esses dados demonstram pela primeira vez que o receptor AT1 é um mediador crítico da hipertrofia dos cardiomiócitos induzida pelo T3, bem como para a ativação da via da Akt, sugerindo que a via Ang I/II-AT1-Akt/GSK-3/mTOR corresponde a um potencial mediador dos efeitos tróficos exercidos pelo T3 nessas células.
Title in English
Angiotensin type 1 receptor mediates Thyroid Hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3ß/mTOR signaling pathway
Keywords in English
Angiotensin receptors
Cardiac hypertrophy
Cardiomyocytes
Interference RNA
Renin angiotensin system
Thyroid hormones
Abstract in English
The present study investigated the role of Angiotensin type 1 receptor (AT1R) in T3-induced cardiomyocyte hypertrophy, as well as the participation of the intracellular mechanisms mediated by AT1R in this cardiac hypertrophy model. The AT1R silencing using small interfering RNA totally prevented the development of T3-induced cardiomyocyte hypertrophy. The cardiomyocytes treated with T3 demonstrated a rapid activation of Akt/GSK-3/mTOR signaling pathway, which was attenuated or prevented by the AT1R silencing. In addition, local Angiotensin I/II (Ang I/II) levels and the AT1R expression were rapidly increased by T3 treatment. These data demonstrate for the first time that the AT1R is a critical mediator to the T3-induced cardiomyocyte hypertrophy, as well as to the activation of the Akt signaling, suggesting that the Ang I/II-AT1R-Akt/GSK-3/mTOR pathway corresponds to a potential mediator of the trophic effect exerted by T3 in cardiomyocytes.
 
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Publishing Date
2010-03-29
 
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