Environmental Toxic Elements and Atherosclerotic Disease: The Epigenetic Connection

Toxic elements (TEs) are widespread environmental contaminants that act as systemic toxicants and are recognized contributors to atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality, posing significant health risks even at low levels of exposure. Increasing evidence indicates that, beyond their direct genotoxic effects, TEs exert pathogenic actions through epigenetic mechanisms that regulate gene expression without altering the underlying DNA sequence. Major epigenetic alterations associated with TE exposure include aberrant DNA methylation and dysregulation of non-coding RNAs, particularly microRNAs (miRNAs). These modifications may disrupt key vascular cellular processes involved in atherogenesis, including endothelial dysfunction, oxidative stress responses, inflammatory signaling, and lipid metabolism, thereby promoting the initiation and progression of atherosclerotic lesions. This literature review examines the epigenetic effects of TEs and highlights their role as potential mediators linking environmental exposures to increased susceptibility to atherosclerosis. Specifically, it summarizes the major classes of TEs, evaluates the evidence associating TE exposure with atherosclerotic cardiovascular outcomes, and discusses the mechanisms through which TE-induced epigenetic alterations may contribute to the development and progression of atherosclerotic disease.