VEGF was first described as vascular permeability factor, a potent inducer of vascular
leakage. Genetic evidence indicates that VEGF-stimulated endothelial proliferation in vitro
and angiogenesis in vivo depend on heparan sulfate, but a requirement for heparan sulfate
in vascular hyperpermeability has not been explored. Here we show that altering endothelial
cell heparan sulfate biosynthesis in vivo decreases hyperpermeability induced by both
VEGF 165 and VEGF 121. Because VEGF 121 does not bind heparan sulfate, the …