The histone demethylase PHF8 represses cardiac hypertrophy upon pressure overload.
Exp Cell Res
; 335(1): 123-34, 2015 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-25921086
ABSTRACT
BACKGROUND:
Mammalian hearts undergo hypertrophy upon pressure overload to support increased workload. Sustained hypertrophy results in cardiac decompensation and subsequently heart failure. The mechanism that prevents the development of cardiac hypertrophy is still not fully understood. Here we elucidate the anti-hypertrophic role of the histone demethylase PHF8. METHODS ANDRESULTS:
PHF8 protein and mRNA levels were down-regulated in human failing hearts, mouse hypertrophic hearts and neonatal rat ventricle myocytes that underwent hypertrophy. Then we generated a cardiac-specific PHF8 transgenic mice, and found that PHF8 overexpression reversed cardiac dysfunction, hypertrophy and fibrosis upon pressure overload. In vivo evidence showed that PHF8 blocked protein synthesis and hypertrophic fetal genes expression. Furthermore, we found that PHF8 inhibited Akt-mTOR pathway in hypertrophic hearts and neonatal rat ventricle myocytes, and rapamycin treatment rescues the effects of PHF8 loss.CONCLUSION:
These results indicate that PHF8 serves as an endogenous factor that the host uses to attenuate cardiac hypertrophy upon cardiac overload. Strategies based on its enhancement might be of benefit in the treatment of hypertrophic cardiomyopathy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Cardiomegalia
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Miócitos Cardíacos
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Histona Desmetilases
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Hipertensão
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2015
Tipo de documento:
Article