Lactylation in Cardiovascular Diseases: Epigenetic Mechanisms and Therapeutic Potential

The global burden of mortality is largely attributable to cardiovascular diseases (CVDs), where altered metabolic homeostasis plays a critical role. The identification of lactylation as an epigenetic modification mediated by lactate has transformed the conventional view of this glycolysis byproduct from a mere metabolic intermediate to a multifaceted signaling molecule. This review comprehensively reveals the mechanistic insights underlying lactylation in CVDs, particularly in myocardial ischemia, atherosclerosis, and heart failure, highlighting its pivotal role in disease pathogenesis through modulation of transcriptional regulation, metabolic adaptation, and cellular differentiation. Considering the enzyme-regulated reversibility of lactylation, this work systematically evaluates its druggable targets, thereby establishing a conceptual foundation for combined metabolism-epigenetic therapeutics.