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Vascular endothelium deploys caveolin-1 to regulate oligodendrogenesis after chronic cerebral ischemia in mice

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Listed:
  • Ying Zhao

    (Medical School of Nanjing University)

  • Wusheng Zhu

    (Medical School of Nanjing University)

  • Ting Wan

    (Air Force Medical University)

  • Xiaohao Zhang

    (Nanjing Medical University)

  • Yunzi Li

    (Medical School of Nanjing University)

  • Zhenqian Huang

    (Medical School of Nanjing University)

  • Pengfei Xu

    (University of Science and Technology of China)

  • Kangmo Huang

    (Medical School of Nanjing University)

  • Ruidong Ye

    (Medical School of Nanjing University)

  • Yi Xie

    (Medical School of Nanjing University)

  • Xinfeng Liu

    (Medical School of Nanjing University
    University of Science and Technology of China)

Abstract

Oligovascular coupling contributes to white matter vascular homeostasis. However, little is known about the effects of oligovascular interaction on oligodendrocyte precursor cell (OPC) changes in chronic cerebral ischemia. Here, using a mouse of bilateral carotid artery stenosis, we show a gradual accumulation of OPCs on vasculature with impaired oligodendrogenesis. Mechanistically, chronic ischemia induces a substantial loss of endothelial caveolin-1 (Cav-1), leading to vascular secretion of heat shock protein 90α (HSP90α). Endothelial-specific over-expression of Cav-1 or genetic knockdown of vascular HSP90α restores normal vascular-OPC interaction, promotes oligodendrogenesis and attenuates ischemic myelin damage. miR-3074(−1)−3p is identified as a direct inducer of Cav-1 reduction in mice and humans. Endothelial uptake of nanoparticle-antagomir improves myelin damage and cognitive deficits dependent on Cav-1. In summary, our findings demonstrate that vascular abnormality may compromise oligodendrogenesis and myelin regeneration through endothelial Cav-1, which may provide an intercellular mechanism in ischemic demyelination.

Suggested Citation

  • Ying Zhao & Wusheng Zhu & Ting Wan & Xiaohao Zhang & Yunzi Li & Zhenqian Huang & Pengfei Xu & Kangmo Huang & Ruidong Ye & Yi Xie & Xinfeng Liu, 2022. "Vascular endothelium deploys caveolin-1 to regulate oligodendrogenesis after chronic cerebral ischemia in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34293-7
    DOI: 10.1038/s41467-022-34293-7
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    References listed on IDEAS

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    1. Brian W. Chow & Vicente Nuñez & Luke Kaplan & Adam J. Granger & Karina Bistrong & Hannah L. Zucker & Payal Kumar & Bernardo L. Sabatini & Chenghua Gu, 2020. "Caveolae in CNS arterioles mediate neurovascular coupling," Nature, Nature, vol. 579(7797), pages 106-110, March.
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