Vascular endothelial growth factor (VEGF) is the founding member of a still
growing family of endothelial cell growth factors. The diverse functions o
f VEGF and its homologues (PIGF, VEGF-B, VEGF-C, VEGF-D, and VEGF-E) can be
explained by their differential binding to the three signaling VEGF recept
ors, The VEGF family members PIGF and VEGF-B with exclusive binding capacit
ies to the VEGFR-1 can influence monocyte activation and differentiation. T
he VEGFR-2 and VEGFR-3 binding VEGF homologues, VEGF-C and VEGF-D, are mito
gens for both vascular and lymphatic endothelial cells. The orf virus encod
ed VEGF-E homologue binds and activates only the VEGFR-2 and thus may be th
e prototype of a vascular endothelial cell-specific growth factor, Further
specific activities of VEGF and its homologues result from receptor-specifi
c signaling and differential expression of ligands or receptors, A naturall
y occurring soluble form of the VEGFR-1 suggests a regulatory role for this
receptor. Finally, the production and activation of factors involved in th
e coagulation/fibrinolytic system provide further evidence for the hypothes
is that processes of hemostasis are involved in angiogenesis.