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Netrins promote developmental and therapeutic angiogenesis.

ABSTRACT: Axonal guidance and vascular patterning share several guidance cues, including proteins in the netrin family. We demonstrate that netrins stimulate proliferation, migration, and tube formation of human endothelial cells in vitro and that this stimulation is independent of known netrin receptors. Suppression of netrin1a messenger RNA in zebrafish inhibits vascular sprouting, implying a proangiogenic role for netrins during vertebrate development. We also show that netrins accelerate neovascularization in an in vivo model of ischemia and that they reverse neuropathy and vasculopathy in a diabetic murine model. We propose that the attractive vascular and neural guidance functions of netrins offer a unique therapeutic potential.

SUBMITTER: Wilson BD

PROVIDER: S-EPMC2577078 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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Netrins promote developmental and therapeutic angiogenesis.

Wilson Brent D BD Ii Masaaki M Park Kye Won KW Suli Arminda A Sorensen Lise K LK Larrieu-Lahargue Fréderic F Urness Lisa D LD Suh Wonhee W Asai Jun J Kock Gerhardus A H GA Thorne Tina T Silver Marcy M Thomas Kirk R KR Chien Chi-Bin CB Losordo Douglas W DW Li Dean Y DY

Science (New York, N.Y.) 20060629 5787

Axonal guidance and vascular patterning share several guidance cues, including proteins in the netrin family. We demonstrate that netrins stimulate proliferation, migration, and tube formation of human endothelial cells in vitro and that this stimulation is independent of known netrin receptors. Suppression of netrin1a messenger RNA in zebrafish inhibits vascular sprouting, implying a proangiogenic role for netrins during vertebrate development. We also show that netrins accelerate neovasculariz ...[more]

PMID: 16809490

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