Evaluation of lung VEGF-A transduction during hyperoxia-induced injury in rats

Background: Since Vascular Endothelial Growth Factor (VEGF) is a main factor for endothelial survival, we evaluated whether VEGF transduction could ameliorate hyperoxiainduced injury, which is associated with predominant endothelial injury. Methods and Results: Transduction (induced 48 hours before hyperoxic exposure) using adenoviral vector (Ad.) for VEGF (10^10 viral particles [VP]) increased moderately survival under hyperoxia (fraction of inspired oxygen [FIO2] >95%) as compared with Ad.Null (10^10 VP) transduction, whereas VEGF transduction with a lower dose (5.10^9 VP) had no effect. After 48 hours of hyperoxia, Ad.VEGF transduction increased lung VEGF concentration, prevented the diffuse loss of capillary bed and induced patchy areas of endothelial cell proliferation (CD31 immunostaining) with interstitial inflammatory cell recruitment as compared to Ad. Null transduction. Hyperoxia was associated with diffuse apoptosis that was inhibited only in patchy areas of endothelial proliferation under VEGF transduction. Hyperoxia-induced alveolar inflammation was similar with Ad.Null and Ad.VEGF. Under normoxia, the high dose of VEGF transduction induced diffuse alveolar inflammation whereas the low dose did not suggesting a pro-inflammatory effect of VEGF that may have participated to increased survival under hyperoxia. Conclusions: We demonstrate that lung VEGF-A transduction despite inhibition of the loss of capillary bed has a marginal effect of on animal survival during hyperoxia-induced injury.