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Cardiovasc. Med."],"abstract":"<jats:p>Atherosclerosis, the principal pathological underpinning of cardiovascular diseases, is a multifaceted process encompassing dysregulated lipid metabolism, chronic inflammation, oxidative stress, aberrant vascular smooth muscle cells (VSMCs) proliferation, and plaque destabilization. Lipocalin-2 (LCN-2), a pivotal member of the lipocalin superfamily, serves as a critical nexus integrating lipid metabolism with inflammatory cascades. This review systematically delineates the gene localization, protein architecture, and expression regulation of LCN-2, with a focus on its multifaceted roles and molecular mechanisms across diverse stages of atherosclerosis, including endothelial dysfunction, lipid deposition, inflammatory amplification, foam cell formation, VSMCs phenotypic switching, and plaque rupture. This work highlights the promise of LCN-2 as a diagnostic biomarker and therapeutic target, offering novel insights and strategic directions for the precise prevention and management of atherosclerosis. Given its pathogenic significance, elevated LCN-2 levels in serum, plasma, urine, and plaque tissue serve as diagnostic and prognostic biomarkers for atherosclerosis. Multiple therapeutic strategies targeting LCN-2, including gene knockout, neutralizing antibodies, small-molecule inhibitors, RNA interference and repurposed clinical drugs, have achieved encouraging anti-atherosclerotic effects in preclinical studies. Collectively, LCN-2 acts as a core molecular linker between inflammation and lipid metabolism in atherosclerosis, and targeting LCN-2 holds great potential for the early diagnosis, risk stratification and novel therapeutic intervention of atherosclerotic cardiovascular diseases.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1927210","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:56:42Z","timestamp":1789977402000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting lipocalin-2 in atherosclerosis: biological functions, pathogenic mechanisms, and therapeutic potential"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhixiang","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The Fourth Affiliated Hospital of Jiangxi University of Chinese Medicine","place":["Nanchang, China"]},{"name":"Department of Critical Care Medicine, 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