title: Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat.
abstract: OBJECTIVE
  We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model.
  
  
  METHODS
  Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test.
  
  
  RESULTS
  CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH.
  
  
  CONCLUSIONS
  Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH.
authors.affiliation: Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Augusto F
authors.initials: AF
authors.lastname: Schmidt
authors.forename: Frances L L
authors.initials: FL
authors.lastname: Gonçalves
authors.forename: Aline C
authors.initials: AC
authors.lastname: Regis
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Gallindo
authors.forename: Lourenço
authors.initials: L
authors.lastname: Sbragia
mesh_terms: D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D010647:Phenyl Ethers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens; D016896:Treatment Outcome; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D010647:Phenyl Ethers; D013723:Teratogens; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D014212:Tretinoin; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C007350:nitrofen