2. Academic Validation
  3. Endothelial major vault protein alleviates vascular remodeling via promoting Parkin-mediated mitophagy

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

  • Nat Commun. 2025 May 10;16(1):4365. doi: 10.1038/s41467-025-59644-y.
Bin Jiang # 1,  Fan Bai # 2,  Yunfu Hu # 2,  Yu Ren 2,  Yuan Su 2,  Wanxuan Song 2,  Kunxin Xie 2,  Dongdong Wang 2,  Junlu Pan 2,  Yuying Liu 2,  Yuxin Feng 3,  Xiaoyu Li 2,  Hanwen Zhang 2,  Xudong Zhu 2,  Hui Bai 2,  Qing Yang 2,  Jingjing Ben 4 5,  Qi Chen 6 7
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. jiangbin@njmu.edu.cn.
  • 2 Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China.
  • 3 Department of Forensic Medicine, Nanjing Medical University, Nanjing, China.
  • 4 Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. bjj@njmu.edu.cn.
  • 5 The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Nanjing, China. bjj@njmu.edu.cn.
  • 6 Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. qichen@njmu.edu.cn.
  • 7 The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China. qichen@njmu.edu.cn.
  • # Contributed equally.
PMID: 40348769 DOI: 10.1038/s41467-025-59644-y
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.

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