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Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado Health Sciences Center, The Children’s Hospital, Denver, Colorado
Submitted 7 September 2004 ; accepted in final form 12 May 2005
VEGF signaling inhibition decreases alveolar and vessel growth in the developing lung, suggesting that impaired VEGF signaling may contribute to decreased lung growth in bronchopulmonary dysplasia (BPD). Whether VEGF treatment improves lung structure in experimental models of BPD is unknown. The objective was to determine whether VEGF treatment enhances alveolarization in infant rats after hyperoxia. Two-day-old Sprague-Dawley rats were placed into hyperoxia or room air (RA) for 12 days. At 14 days, rats received daily treatment with rhVEGF-165 or saline. On day 22, rats were killed. Tissue was collected. Morphometrics was assessed by radial alveolar counts (RAC), mean linear intercepts (MLI), and skeletonization. Compared with RA controls, hyperoxia decreased RAC (6.1 ± 0.4 vs. 11.3 ± 0.4, P < 0.0001), increased MLI (59.2 ± 1.8 vs. 44.0 ± 0.8, P < 0.0001), decreased nodal point density (447 ± 14 vs. 503 ± 12, P < 0.0004), and decreased vessel density (11.7 ± 0.3 vs. 18.9 ± 0.3, P < 0.001), which persisted despite RA recovery. Compared with hyperoxic controls, rhVEGF treatment after hyperoxia increased RAC (11.8 ± 0.5, P < 0.0001), decreased MLI (42.2 ± 1.2, P < 0.0001), increased nodal point density (502 ± 7, P < 0.0005), and increased vessel density (23.2 ± 0.4, P < 0.001). Exposure of neonatal rats to hyperoxia impairs alveolarization and vessel density, which persists despite RA recovery. rhVEGF treatment during recovery enhanced vessel growth and alveolarization. We speculate that lung structure abnormalities after hyperoxia may be partly due to impaired VEGF signaling.
bronchopulmonary dysplasia; lung development; vascular endothelial growth factor; angiogenesis
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