Epigenetics of Cardiomyopathy: Histone Modifications and DNA Methylation

Abstract

Cardiomyopathy is clinically and genetically heterogeneous group of pathologies of myocardium that are being actively studied by researchers. It is now generally accepted that, along with genetic factors, epigenetic mechanisms can be significant in both risk for cardiomyopathy and different clinical manifestations of the disease. This article provides an overview of scientific publications devoted to the study of histone modifications and chromatin remodeling, as well as DNA methylation changes in different types of cardiomyopathy. Most of the reports focused on epigenome profiling of myocardium of patients with dilated cardiomyopathy. The development of cardiomyopathy (dilated, hypertrophic, ischemic, arrhythmogenic, and restrictive) is associated with epigenetic changes of myocardium and this leads to gene expression alteration and metabolic pathways imbalance with pathogenetic significance for heart diseases. The genes of cardiomyopathies (LMNA, TNNI3, ANKRD1, SLC25A4, EYA4, GATAD1, PRDM16, and DMD) are also involved in epigenetic changes of myocardium. Epigenetic modifications, and enzymes that regulate epigenetic processes, are promising for the identification of new molecular markers and metabolic pathways significant for cardiomyopathies, as well as for the development of diagnostic panels and new drugs. At the same time, the high clinical and etiological heterogeneity of cardiomyopathies, a large number of diverse and interrelated epigenetic processes that occur both under physiological conditions and during the pathogenesis of the disease indicate the need to expand epigenetic studies in various forms of cardiomyopathies, including epigenome, transcriptome, and epitranscriptome levels using omics analysis of single cells of myocardium in humans and model animals, as well as in cell lines in disease modeling.