Epigenetics of Cardiomyopathy: Histone Modifications and DNA Methylation

Cardiomyopathies are an actively investigated clinically and genetically heterogeneous group of myocardial pathologies. At present, it is acknowledged that along with genetic factors, epigenetic mechanisms can be of high value in determining both the risk of this pathology and the formation of clinical features of the disease. This review provides an analysis of studies examining histone modifications and chromatin remodeling, as well as alterations in DNA methylation in different forms of cardiomyopathies. Most of the studies in this field are focused on the analysis of the epigenomic profile of myocardial specimens from patients with dilated cardiomyopathy. The development of cardiomyopathy (dilated, hypertrophic, ischemic, restrictive, and arrhythmogenic) is accompanied by changes in the myocardium at the level of epigenetic processes, which leads to alterations in gene expression and an imbalance of metabolic pathways, including those pathogenetically important for the development of heart diseases. Cardiomyopathy genes (LMNA, TNNI3, ANKRD1, SLC25A4, EYA4, GATAD1, PRDM16, and DMD) are also involved in epigenetic alterations occurring in the myocardium. Epigenetic modifications, as well as enzymes that regulate epigenetic processes, are analyzed in terms of the prospects for their use to identify new molecular markers and metabolic pathways that are of value for cardiomyopathies, to develop diagnostic panels and new drugs. At the same time, high clinical and etiological heterogeneity of cardiomyopathies, a large number of diverse and interrelated epigenetic processes that occur both in physiologically normal state and in the disease pathogenesis point to the need to expand epigenetic studies in different forms of cardiomyopathies, including the level of epigenome, transcriptome, and epitranscriptome using omics approaches for the measurements of individual myocardial cells in humans and model animals, as well as in cell lines, in disease modeling.