Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation

Saueressig, Maurício G.; Neto, Amarilio Macedo; Fortis, Elaine A.F.; Westphal, Douglas; Edelweiss, Maria I.A.; Meurer, Luise; Matte, Ursula
April 2008
European Journal of Cardio-Thoracic Surgery;Apr2008, Vol. 33 Issue 4, p717
Academic Journal
Abstract: Objective: To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF165) 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. phVEGF165 (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 VEGF165 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 phVEGF165 compared to none in controls. VEGF gene expression (p <0.01) and VEGF protein expression (p <0.05) were higher in VEGF165-treated bronchi. Conclusions: Local transfection with phVEGF165 promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF165 may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.


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