Induction of pulmonary angiogenesis by adenoviral-mediated gene transfer of vascular endothelial growth factor.
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.
Lambert
Virginie
V
Department of Pediatric Cardiac Surgery, Marie-Lannelongue Hospital, Le-Plessis-Robinson, France. vlambert@ccml.com
Michel
René
R
Mazmanian
Guy-Michel
GM
Dulmet
Elisabeth M
EM
Capderou
André
A
Hervé
Philippe
P
Planché
Claude
C
Serraf
Alain
A
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*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005696:Galactosidases