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
  • Mice
  • Animals
  • Neovascularization, Physiologic*
  • Endothelial Cells/physiology*
  • Muscle, Skeletal/blood supply
  • Chemotaxis
  • Angiogenesis Inducing Agents
  • Cell Line
  • Embryo, Nonmammalian
  • Diabetic Angiopathies/therapy
  • Diabetic Neuropathies/therapy
  • Humans
  • DNA, Complementary
  • Vascular Endothelial Growth Factor A/therapeutic use
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/pharmacology
  • Nerve Growth Factors/physiology*
  • Neural Conduction
  • Endothelium, Vascular/cytology
  • Zebrafish
  • Cell Movement
  • Genetic Therapy
  • Ischemia/drug therapy
  • Receptors, Cell Surface/physiology
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/pharmacology
  • Tumor Suppressor Proteins/physiology*
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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