Lactylation: a metabolic-epigenetic driver in atherosclerosis pathogenesis and therapeutic targeting

Atherosclerosis (AS), a disease of large and medium-sized arteries, is a common cause of cardiovascular morbidity and mortality. Lactylation is a recently identified post-translational modification involving the addition of lactate-derived lactyl groups to lysine residues on proteins. Studies suggest that lactylation plays a vital role in AS development by regulating several key pathological processes. These include inflammation, epithelial-mesenchymal transition, angiogenesis, vascular smooth muscle cell senescence and transdifferentiation, and metabolic dysregulation associated with atherosclerosis. This review summarizes the molecular mechanisms through which lactylation contributes to AS initiation and progression, providing a clearer understanding of the underlying pathophysiological processes. Further elucidation of lactylation may provide novel mechanistic insights into AS development and identify lactylation-targeted interventions as promising strategies to slow AS progression and reduce cardiovascular events.