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The synthesis differentiated lactylation from lactate signaling and distinguished direct evidence in atherosclerosis from findings in other disease models. Predominantly preclinical evidence suggests that both histone and non-histone lactylation are involved in endothelial inflammation, endothelial-to-mesenchymal transition, macrophage polarization and ferroptosis, and vascular smooth muscle cell senescence, phenotypic remodeling, and calcification. Depending on the cellular context, modification site, and downstream targets, lactylation can either promote vascular injury or support anti-inflammatory responses and plaque stabilization. Candidate interventions target lactate production, transport, and lactylation-related enzymes, but their effects often lack specificity for lactylation. Much of the therapeutic evidence originates from non-atherosclerotic models, and clinical validation is currently absent. Therefore, therapeutic development should consider cell type, disease stage, and modification site, with validation of causal mechanisms, selectivity, and safety in atherosclerosis models prior to clinical translation.<\/jats:p>","DOI":"10.17305\/bb.2026.14952","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:59:25Z","timestamp":1792652365000},"source":"Crossref","is-referenced-by-count":0,"title":["Protein lactylation in atherosclerosis \u2013 Mechanisms and therapeutic potential: A narrative review"],"prefix":"10.17305","author":[{"given":"Lijuan","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingquan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daobin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"92136","doi-asserted-by":"crossref","unstructured":"Martin SS, Aday AW, Allen NB, Almarzooq ZI, Anderson CAM, Arora P, et al. 2025 heart disease and stroke statistics: a report of US and global data from the American Heart Association. 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