title: Induction of pulmonary angiogenesis by adenoviral-mediated gene transfer of vascular endothelial growth factor.
abstract: BACKGROUND
  We hypothesized that gene transfer of vascular endothelial growth factor (VEGF) mediated by an adenovirus vector might induce pulmonary artery angiogenesis in a lamb model of pulmonary artery hypoplasia.
  
  
  METHODS
  Thirteen fetal lambs had left pulmonary artery banding at 106 days of gestation. Following birth, 3 groups were divided: VEGF group (n = 5) and beta-GAL group (n = 4) received an adenoviral vector encoding respectively for human VEGF165 and for galactosidase A. A control group (n = 4) had neither gene nor virus. Viral suspensions were selectively instilled in the left bronchus 6.5 days after birth. Five nonoperated lambs constituted the normal group. Euthanasia was performed at 30 days of age. Gene transfer was confirmed by blue coloration of left lung obtained with Xgal solution in an additional experiment. Histomorphometric evaluation was performed. All groups were compared with ANOVA test and paired test was used to compare right and left lung in each animal.
  
  
  RESULTS
  Left lung was similarly hypoplastic in all operated lambs. Left pulmonary artery hypoplasia present in all operated groups was significantly less pronounced in VEGF group. The number of pleural arteries was similarly increased in left lung of all operated lambs. Left lung arterial density was higher in VEGF group than in all other groups. The percentage of parenchyma of left lung was lower in beta-GAL group than in all others, partially returned to normal in VEGF group.
  
  
  CONCLUSIONS
  In this model, transbronchial VEGF gene transfer induces pulmonary angiogenesis, proximal pulmonary artery growth and contributes to lung parenchyma recovery.
authors.affiliation: Department of Pediatric Cardiac Surgery, Marie-Lannelongue Hospital, Le-Plessis-Robinson, France. vlambert@ccml.com
authors.forename: Virginie
authors.initials: V
authors.lastname: Lambert
authors.forename: René
authors.initials: R
authors.lastname: Michel
authors.forename: Guy-Michel
authors.initials: GM
authors.lastname: Mazmanian
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Dulmet
authors.forename: André
authors.initials: A
authors.lastname: Capderou
authors.forename: Philippe
authors.initials: P
authors.lastname: Hervé
authors.forename: Claude
authors.initials: C
authors.lastname: Planché
authors.forename: Alain
authors.initials: A
authors.lastname: Serraf
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005696:Galactosidases / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000002:abnormalities* / Q000473:pathology; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005696:Galactosidases