title: Response of vascular endothelial growth factor and angiogenesis-related genes to stepwise increases in inspired oxygen in neonatal rat lungs.
abstract: BACKGROUND
  Bronchopulmonary dysplasia is an inflammatory lung disease that afflicts preterm infants requiring supplemental oxygen and is associated with impaired pulmonary angiogenesis. We tested the hypothesis that there is a critical threshold of inspired O2 (FiO2) that alters pulmonary angiogenesis.
  
  
  METHODS
  Within 2-6 h of birth, rat pups were exposed to 10%, 21%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% FiO2 for 2 h. Mixed arterial-venous blood gases, serum and pulmonary levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1, and pulmonary angiogenesis gene profiles were determined.
  
  
  RESULTS
  PO2 increased with hyperoxia from 35.6 ± 5.0 (range: 31.5-39.8) at 10% O2 to 108.5 ± 25.0 (range: 82.2-134.8) at 100% O2. PO2 at 21% O2 was 42.4 ± 7.3 (range: 36.8-48.1). Lung VEGF levels declined at 40%-100%. The critical PO2 associated with decreased lung VEGF was 66 mm Hg, achieved with a FiO2 of 0.4. PO2 was inversely correlated with VEGF levels in the lungs (R = -0.377; P < 0.008). Antiangiogenesis genes were robustly upregulated at 70%, predominantly in males. Data are reported as mean ± SD.
  
  
  CONCLUSIONS
  A critical threshold of FiO2 affecting angiogenesis exists in immature lungs. Exposure of preterm lungs to >40% inspired O2, even for 2 h, may result in abnormal expression of biomarkers regulating lung angiogenesis.
authors: Department of Pediatrics, Division of Pulmonology, State University of New York, Downstate Medical Center, Brooklyn, New York, NY, USA.
authors: Michael
authors: M
authors: Keenaghan
authors: Charles L
authors: CL
authors: Cai
authors: Dharmendra
authors: D
authors: Kumar
authors: Gloria B
authors: GB
authors: Valencia
authors: Madu
authors: M
authors: Rao
authors: Jacob V
authors: JV
authors: Aranda
authors: Kay D
authors: KD
authors: Beharry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010100:Oxygen / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen