title: 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.
authors.affiliation: Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Wilson
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.forename: Arminda
authors.initials: A
authors.lastname: Suli
authors.forename: Lise K
authors.initials: LK
authors.lastname: Sorensen
authors.forename: Fréderic
authors.initials: F
authors.lastname: Larrieu-Lahargue
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Urness
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
authors.forename: Jun
authors.initials: J
authors.lastname: Asai
authors.forename: Gerhardus A H
authors.initials: GA
authors.lastname: Kock
authors.forename: Tina
authors.initials: T
authors.lastname: Thorne
authors.forename: Marcy
authors.initials: M
authors.lastname: Silver
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Thomas
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Dean Y
authors.initials: DY
authors.lastname: Li
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D018076:DNA, Complementary; D003925:Diabetic Angiopathies / Q000628:therapy; D003929:Diabetic Neuropathies / Q000628:therapy; D004625:Embryo, Nonmammalian; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000188:drug therapy; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D009431:Neural Conduction; D011956:Receptors, Cell Surface / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use; D015027:Zebrafish
chemical_list: D043925:Angiogenesis Inducing Agents; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D000075385:Netrins; C416214:Ntn4 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D000075388:Netrin-1; C088894:netrin-2