Research Progress on the Effects of Lactylation Modification and m6A Methylation on Programmed Death in...

Programmed cell death (PCD) plays a central regulatory role in the development and progression of cardiovascular diseases (CVD), and its dysregulated activation or inhibition is closely associated with pathological conditions such as myocardial ischemia and atherosclerosis. In recent years, research on epigenetic regulatory mechanisms has advanced rapidly, with lactylation and m6A methylation emerging as key forms of metabolic epigenetic cross-talk. Lactylation utilizes lactate as a substrate and contributes to energy metabolism reprogramming, inflammatory regulation, and cellular stress adaptation by modulating protein lactylation levels, whereas m6A methylation dynamically regulates posttranscriptional splicing, mRNA stability, and translational efficiency through reversible methylation of RNA molecules. Evidence indicates that these two modifications may exert synergistic or antagonistic effects within PCD signaling networks, thereby jointly influencing the initiation and progression of CVD. This review systematically examines the mechanistic interactions between lactylation and m6A methylation in the multiple forms of PCD, including apoptosis, ferroptosis, and pyroptosis, and their roles in CVD, with particular emphasis on their therapeutic feasibility and potential as clinical targets. The aim is to provide theoretical support for uncovering the novel mechanisms of epigenetic metabolic regulation in CVD and to lay the groundwork for precision intervention strategies.