Abstract
Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis of cardiac disease in adults. Investigations using genetic and pharmacologic gain- and loss-of-function approaches have interrogated the function of distinct epigenetic regulators, while the increased deployment of the suite of next-generation sequencing technologies have fundamentally altered our understanding of the genomic targets of these chromatin modifiers. Here, we review recent developments in basic and translational research that have provided tantalizing clues that may be used to unlock the therapeutic potential of the epigenome in heart failure. Additionally, we provide a hypothesis to explain how signal-induced crosstalk between histone tail modifications and long non-coding RNAs triggers chromatin architectural remodeling and culminates in cardiac hypertrophy and fibrosis.
Highlights
Advances in the pharmacologic management of serum lipid levels and surgical, device-aided, and pharmacologic abatement of myocardial ischemia/reperfusion injury have conspired with increases in obesity to exacerbate the epidemic of heart failure across the developed world
The syndrome of heart failure encompasses a spectrum of symptoms with variable manifestation in different people: impaired ability to meet the oxygen demands of the body are accompanied by impaired contractile function of the heart, myocyte hypertrophy, fibrotic deposition and fibroblast to myofibroblast transformation, and/or metabolic derangements
A paradoxical finding from this study was the profound ability of trichostatin A (TSA) to reduce H3 acetylation at many loci. These findings suggest the possibility that HDAC activity controls histone acetyltransferase (HAT) genomic targeting, expression, and/or function in the heart. This mode of crosstalk could explain the seemingly counterintuitive finding that inhibiting enzymes that either add (HAT) or remove (HDAC) acetyl groups can suppress pathogenic processes that contribute to the development of heart failure
Summary
Faculty Reviews are review articles written by the prestigious Members of Faculty Opinions. The articles are commissioned and peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. 1. Assam El-Osta , Central Clinical School, 99 Commercial Road, Level 5, Alfred Centre, Australia. 2. Gianluigi Condorelli, Humanitas Research Hospital, Humanitas University, Rozzano, Milan, Italy. Any comments on the article can be found at the end of the article
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