Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure
| Autor: | Francesco Borgia, Philip Jones, Raffaele De Francesco, Pasquale Gallo, Michael V.G. Latronico, Christian Steinkühler, Paola Gallinari, Paolo Gallo, Serena Grimaldi, Matilde Todaro, Giovanni Esposito, Gianluigi Condorelli, Gennaro Ciliberto |
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| Přispěvatelé: | Gallo, P, Latronico, Mv, Grimaldi, S, Borgia, Francesco, Todaro, M, Jones, P, Gallinari, P, De Francesco, R, Ciliberto, G, Steinkühler, C, Esposito, Giovanni, Condorelli, G., Latronico, MV, Borgia, F, Esposito, G, Condorelli, G |
| Rok vydání: | 2008 |
| Předmět: |
Cardiac function curve
medicine.medical_specialty Hypertrophy Heart failure Physiology medicine.drug_class Biology Peptides Cyclic Histone Deacetylases Cell Line Muscle hypertrophy chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Humans Myocytes Cardiac Enzyme Inhibitors Rats Wistar Cells Cultured Heart Failure Pressure overload Histone deacetylase inhibitor Hypertrophic cardiomyopathy Hypertrophy medicine.disease Rats Histone Deacetylase Inhibitors Disease Models Animal Endocrinology chemistry Echocardiography Heart failure Hypertrophy Left Ventricular Histone deacetylase Cardiology and Cardiovascular Medicine Apicidin |
| Zdroj: | Cardiovascular Research. 80:416-424 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvn215 |
| Popis: | AIMS: 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. METHODS AND RESULTS: The compounds were first analysed in vitro by scoring hypertrophy, expression of foetal genes, and apoptosis of neonatal rat CMs stimulated with phenylephrine, an alpha1-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. CONCLUSION: 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. |
| Databáze: | OpenAIRE |
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