Journal
SCIENCE
Volume 313, Issue 5787, Pages 640-644Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1124704
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Funding
- NHLBI NIH HHS [R01 HL077671-03, R01 HL077671, R01 HL068873] Funding Source: Medline
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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 rote 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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