Reduction of vein graft intimal hyperplasia and preservation of endothelium-dependent relaxation by topical vascular endothelial growth factor.

Abstract

Recent evidence suggests that vascular endothelial growth factor (VEGF), in addition to stimulating angiogenesis, also serves a repair/maintenance or survival function, modulating various aspects of endothelial cell function. This study was designed to examine the effect of VEGF pretreatment in a model of vein graft intimal hyperplasia. Reversed jugular vein-to-common carotid artery interposition grafts were constructed in New Zealand White rabbits. White rabbits. Vein conduits were immersed in solution containing 500 micrograms rhVEGF165 or saline solution for 20 minutes before implantation. Twenty-eight days later the vein grafts and contralateral control jugular veins were harvested for either histologic or isometric tension studies. VEGF-treated vein grafts showed a 23% reduction in intimal area (0.76 +/- 0.07 mm2 vs 0.98 +/- 0.06 mm2; p = 0.028) and a 30% reduction in intimal thickness (62 +/- 6 microns vs 89 +/- 5 microns; p = 0.001) when compared with control grafts. After precontraction with norepinephrine, the maximal relaxation to acetylcholine (endothelium-dependent, receptor-mediated agonist) for control vein grafts was 0%, whereas for VEGF-treated vein grafts it was 25% +/- 9% (p < 0.05 vs control grafts). The maximal relaxation to the calcium ionophore A23187 (endothelium-dependent, receptor-independent agonist) was also greater in VEGF-treated grafts than in control grafts (172.3% +/- 19.4% vs 122.5% +/- 13.7%; p < 0.05). There was no difference in the response to sodium nitroprusside (endothelium-independent agonist) between the two groups. A single topical application of VEGF before implantation reduces intimal hyperplasia and improves endothelial function in a rabbit vein graft model. Further evaluation of this simple strategy to improve vein graft patency appears warranted.