Histone Deacetylases 5 and 9 Govern Responsiveness of the Heart to a Subset of Stress Signals and Play Redundant Roles in Heart Development
| Autor: | James A. Richardson, Chun Li Zhang, Joseph A. Hill, Timothy A. McKinsey, Eric N. Olson, Shurong Chang |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Cardiomegaly Stimulation Histone Deacetylases law.invention Mice Genes Reporter law Internal medicine Mammalian Genetic Models with Minimal or Complex Phenotypes medicine Animals Molecular Biology Mice Knockout Pressure overload Histone deacetylase 5 biology Heart development Calcineurin Myocardium HDAC9 Heart Cell Biology Cell biology Repressor Proteins Histone Endocrinology Mutation cardiovascular system biology.protein Suppressor Carrier Proteins |
| Zdroj: | Molecular and Cellular Biology. 24:8467-8476 |
| ISSN: | 1098-5549 |
| Popis: | The adult heart responds to stress signals by hypertrophic growth, which is often accompanied by activation of a fetal cardiac gene program and eventual cardiac demise. We showed previously that histone deacetylase 9 (HDAC9) acts as a suppressor of cardiac hypertrophy and that mice lacking HDAC9 are sensitized to cardiac stress signals. Here we report that mice lacking HDAC5 display a similar cardiac phenotype and develop profoundly enlarged hearts in response to pressure overload resulting from aortic constriction or constitutive cardiac activation of calcineurin, a transducer of cardiac stress signals. In contrast, mice lacking either HDAC5 or HDAC9 show a hypertrophic response to chronic beta-adrenergic stimulation identical to that of wild-type littermates, suggesting that these HDACs modulate a specific subset of cardiac stress response pathways. We also show that compound mutant mice lacking both HDAC5 and HDAC9 show a propensity for lethal ventricular septal defects and thin-walled myocardium. These findings reveal central roles for HDACs 5 and 9 in the suppression of a subset of cardiac stress signals as well as redundant functions in the control of cardiac development. |
| Databáze: | OpenAIRE |
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