Age-dependent impairment of reendothelialization after arterial injury: role of vascular endothelial growth factor.

The mechanisms responsible for the association between advanced age and atherosclerotic diseases are not clear. Because atherosclerosis develops in response to local endothelial injuries, we investigated the effect of aging on vascular healing and reendothelialization. Endothelium denudation was performed by balloon angioplasty of the iliac arteries in young and old New Zealand White rabbits. Planimetric analysis after Evans Blue staining at 28 days after injury showed a significant decrease in reendothelialization in old versus young animals, which was associated with an important increase in neointimal formation in old rabbits. Vascular endothelial growth factor (VEGF) was rapidly induced after balloon injury. However, arterial VEGF expression was significantly reduced in old versus young animals. To confirm the role of VEGF in the age-dependent impairment of reendothelialization, an adenoviral vector encoding for VEGF(165) (adeno-VEGF) was locally delivered at the time of iliac artery angioplasty. Compared with animals treated with the control vector (adeno-betaGal), reendothelialization was significantly improved and neointimal formation reduced in old rabbits treated with adeno-VEGF. These results document for the first time an age-dependent impairment of reendothelialization after arterial injury. Our study indicates that VEGF supplementation may represent a useful strategy to accelerate reendothelialization and improve vascular healing in the context of aging.