The effect of vascular endothelial growth factor on angiogenesis: an experimental study.

OBJECTIVE: to evaluate the effects of exogenous vascular endothelial growth factor (VEGF) on angiogenesis in a rabbit model of persistent hind limb ischaemia. MATERIALS AND METHODS: ischaemia was induced in the hind limbs of 42 New Zealand white rabbits divided into six groups, each of 7 animals. Group 1a and 1b received intramuscular injections of 1 and 2 mg VEGF/day, respectively, into the ischaemic hind limb for 10 days beginning on postoperative 11th day, and group 1c received IM injections of saline only. Group 2a and 2b received similar regimen of VEGF, but administered intra-arterially. Group 2c served as controls. Perfusion of the ischaemic limb was evaluated by thigh blood pressure and thigh circumference at 10, 25 and 40 days following limb ischaemia in all animals and by digital subtraction angiography, perfusion scans, histological examination of capillary density in 2 animals from each group. RESULTS: thigh pressure index and thigh circumference improved significantly in the VEGF treated animals (Groups 1a,b and 2a,b). Collateral formation, as assessed by angiography, scintigraphy and by histological examination, indicated marked formation of collaterals in the VEGF treated animals as compared with the controls. This was most pronounced in groups receiving the highest dose of VEGF. CONCLUSION: these data suggest that VEGF promotes angiogenesis, that the route of administration is unimportant, but that a dose-response relationship is present in this experimental ischaemic hind limb model.