Protein lactylation influences atherosclerotic plaque stability by regulating macrophage functions.

Atherosclerosis (AS) is a leading cause of cardiovascular events and mortality worldwide. Plaque stability is a direct determinant of clinical outcomes for patients. Within the hypoxic and inflammatory microenvironment of plaques, glycolysis is significantly enhanced in macrophages and other cells, leading to substantial lactate accumulation. Recent studies reveal that lactate serves not only as a metabolic byproduct but also as a substrate for a novel post-translational modification, driving dynamic reversible protein lactylation. This review systematically demonstrates that protein lactylation acts as a critical molecular bridge, linking cellular metabolic dysregulation to immune-inflammatory responses. It precisely regulates multiple macrophage functions, such as polarization, programmed cell death, and phagocytic efficiency. Through these mechanisms, it profoundly influences key pathological processes. These processes include plaque inflammation and repair, necrotic core formation, and local thrombogenesis. Ultimately, protein lactylation emerges as a pivotal regulatory mechanism governing the stability and evolution of AS plaques. Furthermore, this review explores potential therapeutic strategies targeting this modification network, aiming to advance the clinical translation of related research.