PUBLICATION

Netrins Promote Developmental and Therapeutic Angiogenesis

Authors
Wilson, B.D., Ii, M., Park, K.W., Suli, A., Sorensen, L.K., Larrieu-Lahargue, F., Urness, L.D., Suh, W., Asai, J., Kock, G.A., Thorne, T., Silver, M., Thomas, K.R., Chien, C.B., Losordo, D.W., and Li, D.Y.
ID
ZDB-PUB-060703-18
Date
2006
Source
Science (New York, N.Y.)   313(5787): 640-644 (Journal)
Registered Authors
Chien, Chi-Bin, Suli, Arminda
Keywords
none
MeSH Terms
  • Endothelial Cells/physiology*
  • DNA, Complementary
  • Mice
  • Cell Movement
  • Embryo, Nonmammalian
  • Receptors, Cell Surface/physiology
  • Zebrafish
  • Diabetic Angiopathies/therapy
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/pharmacology
  • Tumor Suppressor Proteins/physiology*
  • Animals
  • Muscle, Skeletal/blood supply
  • Ischemia/drug therapy
  • Diabetic Neuropathies/therapy
  • Neural Conduction
  • Humans
  • Neovascularization, Physiologic*
  • Vascular Endothelial Growth Factor A/therapeutic use
  • Genetic Therapy
  • Angiogenesis Inducing Agents
  • Cell Line
  • Chemotaxis
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/pharmacology
  • Nerve Growth Factors/physiology*
  • Endothelium, Vascular/cytology
PubMed
16809490 Full text @ Science
Abstract
Axonal guidance and vascular patterning share several guidance cues, including proteins of the netrin family. We demonstrate that netrins stimulate the proliferation, migration and tube formation of human endothelial cells in vitro, and that this stimulation is independent of known netrin receptors. Knockdown of netrin1a mRNA in zebrafish inhibits vascular sprouting, implying a pro-angiogenic 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.
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