Epigenetic and Nongenomic Roles for Histone Deacetylases in Heart Failure

Heart failure due to systolic and/or diastolic ventricular dysfunction afflicts millions of people worldwide. Most heart failure drugs target signaling cascades that emanate from the cardiomyocyte cell surface. However, given the ability of numerous receptors to trigger adverse ventricular remodeling, it has been hypothesized that more efficacious therapeutic strategies would be based on inhibition of downstream “nodal” points that integrate upstream signals to convey a common pathway for heart failure pathogenesis. This chapter highlights data suggesting that a family of epigenetic regulatory enzymes, histone deacetylases (HDACs), represent such nodal points. We discuss recent findings that illustrate how HDACs not only control cardiac gene expression via epigenetic regulation, but also serve crucial non-genomic functions in the heart through deacetylation of non-histone proteins.