PMID- 31994601
OWN - NLM
STAT- MEDLINE
DCOM- 20200407
LR  - 20211204
IS  - 1414-431X (Electronic)
IS  - 0100-879X (Print)
IS  - 0100-879X (Linking)
VI  - 53
IP  - 2
DP  - 2020
TI  - Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis 
      pathways.
PG  - e8793
LID - S0100-879X2020000200602 [pii]
LID - 10.1590/1414-431X20198793 [doi]
LID - e8793
AB  - 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.
FAU - Zhao, Zhengbo
AU  - Zhao Z
AUID- ORCID: 0000-0003-2613-2397
AD  - Department of Cardiovascular Medicine, Jiulongpo District People's Hospital, 
      Chongqing, China.
FAU - Liu, Han
AU  - Liu H
AUID- ORCID: 0000-0002-0477-1537
AD  - Department of Neurology, Jiulongpo District People's Hospital, Chongqing, China.
FAU - Guo, Dongmei
AU  - Guo D
AUID- ORCID: 0000-0002-7332-380X
AD  - Department of Cardiovascular Medicine, Nanchuan District People's Hospital, 
      Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20200124
PL  - Brazil
TA  - Braz J Med Biol Res
JT  - Brazilian journal of medical and biological research = Revista brasileira de 
      pesquisas medicas e biologicas
JID - 8112917
RN  - 0 (Amides)
RN  - 0 (Fumarates)
RN  - 11128-99-7 (Angiotensin II)
RN  - 502FWN4Q32 (aliskiren)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Amides/*administration & dosage
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cardiomegaly/chemically induced/metabolism/*prevention & control
MH  - Disease Models, Animal
MH  - Fibrosis/chemically induced/prevention & control
MH  - Flow Cytometry
MH  - Fumarates/*administration & dosage
MH  - Isoproterenol/pharmacology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/drug effects/*metabolism
PMC - PMC6984373
EDAT- 2020/01/30 06:00
MHDA- 2020/04/09 06:00
PMCR- 2020/01/24
CRDT- 2020/01/30 06:00
PHST- 2019/06/16 00:00 [received]
PHST- 2019/10/21 00:00 [accepted]
PHST- 2020/01/30 06:00 [entrez]
PHST- 2020/01/30 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2020/01/24 00:00 [pmc-release]
AID - S0100-879X2020000200602 [pii]
AID - 10.1590/1414-431X20198793 [doi]
PST - epublish
SO  - Braz J Med Biol Res. 2020 Jan 24;53(2):e8793. doi: 10.1590/1414-431X20198793. 
      eCollection 2020.