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A new role for Nogo as a regulator of vascular remodeling

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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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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