iProXProteomicsMi LiuRattus Norvegicushttp://www.iprox.org/page/project.html?id=IPX0013498000liumi@smu.edu.cnThe Eighth Affiliated Hospital, Southern Medical University (The First People’ s Hospital of Shunde, Foshan)iProXfalseLCN2 Attenuates Vascular Calcification by Stabilizing Acadvl to Enhance Fatty Acid OxidationVascular calcification (VC) is a critical contributor to cardiovascular mortality, driven by osteogenic differentiation of vascular smooth muscle cells (VSMCs) under hyperphosphatemia, yet molecular mechanisms remain incompletely defined. This study investigates the role of lipocalin-2 (LCN2) in regulating VC through both clinical and experimental approaches. We found LCN2 expression was significantly downregulated in calcified radial arteries from chronic kidney disease (CKD) patients and in VSMCs under calcifying conditions. Functionally, recombinant LCN2 protein or LCN2 overexpression attenuated calcification in VSMCs, arterial rings, and a CKD-associated VC mouse model, while LCN2 knockdown exacerbated these effects. Multi-omics analysis revealed that LCN2 enhanced fatty acid β-oxidation (FAO), and pharmacological inhibition of FAO accelerated calcification. Mechanistic studies using co-immunoprecipitation mass spectrometry combined with computational modeling identified a direct and stable interaction beFri Sep 19 00:00:00 BST 2025PXD06863710116