Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure.

Matilde Todaro, Pasquale Gallo, Michael V.G. Latronico, Philip Jones, Gennaro Ciliberto, Giovanni Esposito, Paolo Gallo, Francesco Borgia, Gianluigi Condorelli, Paolo Gallo, Christian Steinkühler, Raffaele De Francesco, Paola Gallinari, Serena Grimaldi, Matilde Todaro

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123 Citazioni (Scopus)


Recent studies have demonstrated the importance of chromatin remodelling via histone acetylation/deacetylation for the control of cardiac gene expression. Specific histone deacetylases (HDACs) can, in fact, play a positive or negative role in determining cardiac myocyte (CM) size. Here, we report on the effect on hypertrophy development of three inhibitors (HDACi) of class I HDACs.The compounds were first analysed in vitro by scoring hypertrophy, expression of foetal genes, and apoptosis of neonatal rat CMs stimulated with phenylephrine, an alpha 1-adrenergic agonist. This initial screening indicated that a truncated derivative of apicidin with class I HDAC specificity, denoted API-D, had the highest efficacy to toxicity ratio, and was thus selected for further analysis in vivo. Administration of this drug significantly decreased myocardial hypertrophy and foetal gene expression after 1 week of pressure overload induced by thoracic aortic constriction (TAC) in mice. After 9 weeks of TAC, when manifest heart failure is encountered, mice treated with API-D presented with significantly improved echocardiographic and haemodynamic parameters of cardiac function when compared with untreated TAC-operated mice.The apicidin derivative, API-D, is capable of reducing hypertrophy and, consequently, the transition to heart failure in mice subjected to TAC. Treatment with this substance, therefore, holds promise as an important therapeutic option for heart failure.
Lingua originaleEnglish
pagine (da-a)416-424
Numero di pagine9
RivistaCardiovascular Research
Stato di pubblicazionePublished - 2008

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2700.2705???
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