Endothelial major vault protein alleviates vascular remodeling via promoting Parkin-mediated mitophagy

Bin Jiang (), Fan Bai, Yunfu Hu, Yu Ren, Yuan Su, Wanxuan Song, Kunxin Xie, Dongdong Wang, Junlu Pan, Yuying Liu, Yuxin Feng, Xiaoyu Li, Hanwen Zhang, Xudong Zhu, Hui Bai, Qing Yang, Jingjing Ben () and Qi Chen ()
Additional contact information
Bin Jiang: Nanjing Medical University
Fan Bai: Nanjing Medical University
Yunfu Hu: Nanjing Medical University
Yu Ren: Nanjing Medical University
Yuan Su: Nanjing Medical University
Wanxuan Song: Nanjing Medical University
Kunxin Xie: Nanjing Medical University
Dongdong Wang: Nanjing Medical University
Junlu Pan: Nanjing Medical University
Yuying Liu: Nanjing Medical University
Yuxin Feng: Nanjing Medical University
Xiaoyu Li: Nanjing Medical University
Hanwen Zhang: Nanjing Medical University
Xudong Zhu: Nanjing Medical University
Hui Bai: Nanjing Medical University
Qing Yang: Nanjing Medical University
Jingjing Ben: Nanjing Medical University
Qi Chen: Nanjing Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Many important vascular diseases including neointimal hyperplasia and atherosclerosis are characterized by the endothelial cell (EC) injury-initiated pathological vascular remodeling. However, the endogenous regulatory mechanisms underlying it are not fully understood. The present study investigates regulatory role of major vault protein (MVP) in the pathogenesis of vascular remodeling via controlling EC injury. By generating male murine vascular disease models, we find that ablation of endothelial MVP increases neointima formation and promotes atherosclerosis. Mechanistically, MVP directly binds with Parkin and inhibits the ubiquitination and proteasomal degradation of Parkin by dissociating the E3 ligase NEDD4L from Parkin, leading to activation of Parkin-mediated mitophagy pathway in the EC. Genetic modulation of endothelial MVP and Parkin influences the mitophagy, apoptosis, and neointima formation. These results demonstrate that MVP acts as an intracellular regulator promoting Parkin-mediated mitophagy. Our findings suggest that MVP/NEDD4L/Parkin axis may serve as the therapeutic target for treating intimal hyperplasia and atherosclerosis.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59644-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59644-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59644-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().