CVDs arise from the interplay of multiple factors, with genetics and environmental exposures representing key drivers. Accumulating evidence over recent decades has unequivocally established that epigenetic modifications, most prominently DNA methylation, play a pivotal, non-redundant role in the initiation, development, and progression of CVDs. As a critical molecular bridge linking genetic predisposition, environmental insults, and the pathogenesis of CVDs, DNA methylation dynamically mediates crosstalk among these three components, thereby emerging as a core focus for dissecting the underlying pathological mechanisms of CVDs. Thus, this review summarizes the functional roles of DNA methylation in common CVDs, including coronary heart disease (CHD), hypertension, and heart failure (HF). Special emphasis is placed on the regulatory mechanisms of DNA methylation in driving disease pathogenesis, as well as the associated translational potential for preventing CVDs and for clinical management. Moreover, this review delineates the specific pathways through which DNA methylation modulates CVDs onset and progression—providing a novel perspective for in-depth investigation of disease etiologies—and offers a robust theoretical basis for identifying novel therapeutic targets for CVDs. Ultimately, these insights aim to lay a foundation for the optimization and innovation of clinical diagnostic and therapeutic strategies for CVDs.
Chen et al. (2026) studied this question.