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Abstract: TH-PO0278

Lipocalin-2 Ameliorates CKD-Associated Vascular Calcification Through Promoting Fatty Acid β Oxidation

Session Information

Category: Hypertension and CVD

  • 1601 Hypertension and CVD: Basic

Authors

  • Liu, Mi, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Guangdong, China
  • Dou, Xianrui, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Guangdong, China
Background

Vascular calcification (VC) is common in chronic kidney disease (CKD) patients, driven primarily by osteogenic transformation of vascular smooth muscle cells (VSMCs). Lipocalin-2 (LCN2), a secreted protein implicated in atherosclerosis and abdominal aortic aneurysm, but its role and mechanism in CKD-associated VC remains unclear.

Methods

The effects of LCN2 on vascular calcification were explored in vitro and in vivo. Transcriptome sequencing, proteomics, co-immunoprecipitation mass spectrum and molecular docking were performed to investigate the mechanism by which LCN2 plays a role in VC.

Results

LCN2 was downregulated in CKD patients with VC and high-phosphorus-treated VSMCs. Recombinant LCN2 reduced calcification and osteogenic differentiation in VSMCs, while LCN2 knockdown worsened it. In CKD mice, AAV-mediated LCN2 overexpression alleviated aortic calcification. Multi-omics revealed LCN2 activates fatty acid β-oxidation by binding with very long-chain acyl-CoA dehydrogenase (Acadvl). Acadvl knockdown exacerbated calcification and diminished LCN2's protective effects.

Conclusion

LCN2 interacts with Acadvl and then enhances fatty acid β-oxidation, thus ameliorating CKD-associated VC, which offers a novel therapeutic target against VC.

Figure 1. Overexpression of LCN2 improved aortic vascular calcification and inhibited osteogenic differentiation in mice.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)