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A new role for Nogo as a regulator of vascular remodeling

Nature Medicine volume 10, pages 382–388 (2004)Cite this article

Abstract

Although Nogo-A has been identified in the central nervous system as an inhibitor of axonal regeneration, the peripheral roles of Nogo isoforms remain virtually unknown. Here, using a proteomic analysis to identify proteins enriched in caveolae and/or lipid rafts (CEM/LR), we show that Nogo-B is highly expressed in cultured endothelial and smooth muscle cells, as well as in intact blood vessels. The N terminus of Nogo-B promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle (VSM) cells, processes necessary for vascular remodeling. Vascular injury in Nogo-A/B-deficient mice promotes exaggerated neointimal proliferation, and adenoviral-mediated gene transfer of Nogo-B rescues the abnormal vascular expansion in those knockout mice. Our discovery that Nogo-B is a regulator of vascular homeostasis and remodeling broadens the functional scope of this family of proteins.

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Figure 1: Identification of Nogo-B in vascular cells.
Figure 2: The N terminus of Nogo-B promotes vascular cell adhesion.
Figure 3: Am-Nogo-B is a chemoattractant for HUVECs.
Figure 4: Nogo-B is present in intact blood vessels.
Figure 5: Evidence supporting a role for Nogo in vascular remodeling.
Figure 6: Reconstitution with Ad-Nogo-B prevents injury-induced neointimal expansion in Nogo-A/B-deficient mice.

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Acknowledgements

This work is supported by grants to W.C.S. from the National Heart, Lung and Blood Institute, and to P.T. from the National Cancer Institute.

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Author notes

  1. Lisette Acevedo and Jun Yu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology and Program in Vascular Cell Signaling and Therapeutics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, 06536, Connecticut, USA

    Lisette Acevedo, Jun Yu, Robert Qing Miao, David Fulton & William C Sessa

  2. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Hediye Erdjument-Bromage & Paul Tempst

  3. Neurology and Neurobiology, Yale University School of Medicine, New Haven, 06536, Connecticut, USA

    Ji-Eun Kim & Stephen M Strittmatter

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  1. Lisette Acevedo
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Correspondence to William C Sessa.

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Acevedo, L., Yu, J., Erdjument-Bromage, H. et al. A new role for Nogo as a regulator of vascular remodeling. Nat Med 10, 382–388 (2004). https://doi.org/10.1038/nm1020

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