Many failures of vascular reconstructions are due to thrombosis and re
stenosis and are often attributed to inadequate endothelial regenerati
on at the site of endothelial denudation. Vascular permeability factor
(VPF) is a naturally occurring growth factor responsible for vessel p
ermeability and microvascular angiogenesis. Here, we show that VPF sti
mulated rabbit endothelial cell proliferation in vitro at concentratio
ns 100 ng/ml. However, VPF had no effect on smooth muscle cell prolife
ration at these concentrations up to 500 ng/ml. When VPF was administe
red for 4 weeks (120 mu g, twice weekly, i.v.) following balloon angio
plasty-induced endothelial denudation of rabbit carotid artery, there
was a significant increase in the in vivo regeneration of endothelium
compared to control (57.5 +/- 6.7% vs. 38.3 +/- 1.9%, P < 0.01). Moreo
ver, 8 weeks of VPF administration resulted in 88.1 +/- 3.1% re-endoth
elialization compared to control (44.7 +/- 3.8%). Hence, VPF appears t
o be a specific mitogen for endothelial regeneration.