PXD068638

PXD068638 is an original dataset announced via ProteomeXchange.

Title	Lipocalin-2 Attenuates Vascular Calcification by Stabilizing Acadvl to Enhance Fatty Acid Oxidation
Description	Vascular 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 between LCN2 and very long-chain acyl-CoA dehydrogenase (Acadvl), a key mitochondrial FAO enzyme. We demonstrated that LCN2 stabilized Acadvl and enhanced its expression, while Acadvl knockdown abolished LCN2's protective effects against VC. These findings establish the LCN2-Acadvl axis as a novel regulatory mechanism mitigating VC through enhancing FAO, revealing promising therapeutic targets for vascular calcification pathology.
HostingRepository	iProX
AnnounceDate	2025-09-19
AnnouncementXML	Submission_2026-07-01_00:57:54.870.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiulin Li
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-22 00:04:38	ID requested
⏵ 1	2026-07-01 00:57:55	announced

Dataset with its publication pending

submitter keyword: LCN2, Vascular Calcification, fatty acid β oxidation, Acadvl, vascular smooth muscle cells

Mi Liu
contact affiliation	The Eighth Affiliated Hospital, Southern Medical University (The First People’ s Hospital of Shunde, Foshan)
contact email	liumi@smu.edu.cn
lab head
Xiulin Li
contact affiliation	The Eighth Affiliated Hospital, Southern Medical University (The First People’ s Hospital of Shunde, Foshan)
contact email	xiulinl99@163.com
dataset submitter

iProX dataset URI