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Pediatr Res. 2017 Oct;82(4):642-649. doi: 10.1038/pr.2017.126. Epub 2017 Jun 21.

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

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Department of Pharmacology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado.
Division of Cardiology, Department of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado.
Division of Cardiology, Department of Medicine, Denver Health and Hospital Authority, Denver, Colorado.
Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado.


BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies.

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