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 modifications 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. The aim of this literature review is to critically examine the evidence linking TE exposure to atherosclerosis, with a particular focus on the potential role of epigenetic mechanisms in mediating this association. Specifically, it summarizes the epidemiological evidence linking TE exposure to ASCVD, discusses the mechanisms through which TE-induced epigenetic alterations may contribute to the development and progression of atherosclerotic disease, and critically evaluates the strengths and limitations of the available evidence to identify priorities for future research.