Abstract
INTRODUCTION: Cardiac hypertrophy and fibrotic scarring are fundamental contributors to the progression of heart failure and are associated with poor clinical outcomes. Recent advancements in cardiovascular research have emphasized the central role of epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, in regulating the gene expression changes underlying these pathological processes. METHODS: A comprehensive literature review was conducted using databases, including PubMed, Scopus, and Web of Science. Predefined keywords and inclusion/exclusion criteria were applied to select relevant studies focusing on epigenetic regulation in cardiac hypertrophy and fibrosis. Particular attention was given to studies involving DNA methyltransferases, TET enzymes, histone deacetylases, demethylases, chromatin remodeling complexes, and non-coding RNAs. Methodological transparency was ensured through a structured screening and data extraction process. RESULTS: The review highlights the dynamic regulation of cardiac gene expression by epigenetic factors. DNA methylation and demethylation influence fibroblast activation and extracellular matrix deposition. Histone-modifying enzymes reshape chromatin architecture, altering transcriptional accessibility. Chromatin remodeling complexes regulate nucleosome positioning during stress responses. Emerging insights into epigenetic memory and transgenerational epigenetic inheritance further reveal the heritable nature of disease susceptibility. DISCUSSION: These epigenetic perturbations collectively orchestrate the maladaptive gene expression patterns seen in cardiac hypertrophy and fibrosis. Understanding their roles provides a mechanistic basis for identifying biomarkers and therapeutic targets. The review also discusses recent omics-based technologies that aid in the characterization of epigenetic alterations, thereby expanding diagnostic and therapeutic horizons. CONCLUSION: Epigenetic mechanisms are pivotal in the development and progression of cardiac hypertrophy and fibrosis. Advances in epigenomic profiling are facilitating the development of precise and targeted interventions. This review underscores the potential of epigenetic therapies and calls for intensified research efforts to translate these findings into clinical applications.