Epigenetics of Heart Development and Disease

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, accounting for approximately 31% of global mortality. Despite advances in diagnosis, prevention, and treatment, the prevalence of CVD continues to rise, highlighting that traditional risk factors (hypertension, diabetes, and dyslipidemia) do not fully explain disease susceptibility. Epigenetics, defined as heritable modifications of gene expression independent of DNA sequence changes, has emerged as a critical factor influencing cardiovascular health and development. This regulation involves dynamic changes in chromatin structure through chromatin remodeling and DNA and histone chemical modifications, as well as the regulatory functions of noncoding RNAs. Epigenetic mechanisms modulate gene expression programs essential for cardiovascular development and response to injury, linking environmental exposures to disease onset and progression. Epigenetic dysregulation has been implicated in heart failure (HF) pathogenesis, often exacerbated by comorbid conditions like diabetes. Understanding epigenetic contributions offers promising avenues for novel therapeutic strategies targeting these molecular pathways. This chapter focuses on the evolving role of epigenetics as a key nongenetic determinant of cardiac development and heart failure.