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Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways
Zhao, Zhengbo; Liu, Han; Guo, Dongmei.
  • Zhao, Zhengbo; Jiulongpo District People's Hospital. Department of Cardiovascular Medicine. CN
  • Liu, Han; Jiulongpo District People's Hospital. Department of Neurology. CN
  • Guo, Dongmei; Nanchuan District People's Hospital. Department of Cardiovascular Medicine. CN
Braz. j. med. biol. res ; 53(2): e8793, 2020. tab, graf
Article in English | LILACS | ID: biblio-1055493
ABSTRACT
Aliskiren (ALS) is well known for its antihypertensive properties. However, the potential underlying the molecular mechanism and the anti-hypertrophic effect of ALS have not yet been fully elucidated. The aim of the present study was to investigate the role of ALS in mammalian target of rapamycin (mTOR) and apoptosis signaling using in vivo and in vitro models of cardiac hypertrophy. A rat model of cardiac hypertrophy was induced by isoproterenol treatment (5 mg·kg-1·day-1) for 4 weeks, with or without ALS treatment at 20 mg·kg-1·day-1. The expression of hypertrophic, fibrotic, and apoptotic markers was determined by RT-qPCR. The protein expression of apoptotic markers mTOR and p-mTOR was assessed by western blot analysis. The proliferation of H9C2 cells was monitored using the MTS assay. Cell apoptosis was analyzed using flow cytometry. In vivo, isoproterenol-treated rats exhibited worse cardiac function, whereas ALS treatment reversed these dysfunctions, which were associated with changes in p-mTOR, Bcl-2, Bax, and cleaved caspase-3 expression, as well as the number of apoptotic cells. In vitro, H9C2 cardiomyocyte viability was significantly inhibited and cardiac hypertrophy was induced by Ang II administration, but ALS reversed Ang II-induced H9C2 cardiomyocyte hypertrophy and death. Furthermore, Ang II triggered the activation of the mTOR and apoptosis pathways in hypertrophic cardiomyocytes that were inhibited by ALS treatment. These results indicated that ALS alleviated cardiac hypertrophy through inhibition of the mTOR and apoptosis pathways in cardiomyocytes.
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Full text: Available Index: LILACS (Americas) Main subject: Apoptosis / Cardiomegaly / TOR Serine-Threonine Kinases / Fumarates / Amides Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2020 Type: Article Affiliation country: China Institution/Affiliation country: Jiulongpo District People's Hospital/CN / Nanchuan District People's Hospital/CN

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Full text: Available Index: LILACS (Americas) Main subject: Apoptosis / Cardiomegaly / TOR Serine-Threonine Kinases / Fumarates / Amides Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2020 Type: Article Affiliation country: China Institution/Affiliation country: Jiulongpo District People's Hospital/CN / Nanchuan District People's Hospital/CN