Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review)

Atherosclerosis (AS) is the principal pathological basis of cardiovascular disease and develops through the coordinated progression of endothelial dysfunction, lipid accumulation, macrophage foam‑cell formation, vascular smooth muscle cell remodeling, chronic inflammation and plaque destabilization. Protein post‑translational modifications (PTMs) provide a reversible regulatory layer through which metabolic, oxidative, inflammatory and mechanical cues are translated into changes in protein activity, stability, localization and molecular interactions. In this review, the roles of major PTMs in AS were summarized, including lysine modifications, cysteine modifications, phosphorylation, glycosylation, nitration and ADP‑ribosylation. Rather than treating these modifications as isolated events, their integration into disease‑related regulatory networks is emphasized. In particular, lysine lactylation is discussed as a metabolic‑epigenetic mechanism linking lactate accumulation to endothelial dysfunction, macrophage polarization, vascular smooth muscle cell senescence and vascular calcification. PTM crosstalk is also highlighted, including SUMOylation‑ubiquitination and ubiquitination‑phosphorylation interactions, as a mechanism that coordinates inflammasome activation, oxidative stress and vascular cell phenotypic switching. Finally, the therapeutic potential of targeting PTM‑related enzymes and pathways, such as histone deacetylases, poly(ADP‑ribose) polymerases, kinases and palmitoylation regulators was evaluated, while addressing key challenges including context‑dependent PTM effects, limited site‑specific validation, insufficient human plaque evidence and the translational gap between experimental findings and clinical application. This review provides an integrated framework for understanding PTM‑mediated regulation in AS and for developing more precise PTM‑based therapeutic strategies.