Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation.
OBJECTIVE
To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation.


METHODS
To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens.


RESULTS
Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi.


CONCLUSIONS
Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.
Saueressig
Maurício G
MG
Lung and Airway Laboratory, Federal University of Rio Grande do Sul School of Medicine, Hospital de Clínicas de Porto Alegre, Brazil. msaueressig@hcpa.ufrgs.br
Neto
Amarilio Macedo
AM
Fortis
Elaine A F
EA
Westphal
Douglas
D
Edelweiss
Maria I A
MI
Meurer
Luise
L
Matte
Ursula
U
D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001981:Bronchial Arteries / Q000502:physiology*; D004285:Dogs; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use
D043925:Angiogenesis Inducing Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A