Effect of recombinant adeno-associated virus vector-mediated vascular endothelial growth factor gene transfer on wound healing after burn injury
| Autor: | Mariarosaria Galeano, Herbert Marini, Valerio Torre, Paolo Seminara, Margherita Calò, Francesco Stagno d'Alcontres, Giovanni Squadrito, Domenica Altavilla, Venuti Fs, Barbara Deodato, Patrizia Lo Cascio, Mauro Giacca, Francesco Squadrito, Michele R. Colonna |
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| Přispěvatelé: | M., Galeano, B., Deodato, D., Altavilla, G., Squadrito, P., Seminara, H., Marini, F. S., D'Alcontre, M., Colonna, M., Calò, P. L., Cascio, V., Torre, Giacca, Mauro, F. S., Venuti, F., Squadrito |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Burn injury viruses Genetic enhancement genetics/metabolism Nitric Oxide Synthase Type II Endothelial Growth Factors partial thickness burn Inbred C57BL Critical Care and Intensive Care Medicine medicine.disease_cause metabolism/pathology/physiopathology/therapy Dependovirus Endothelial Growth Factor metabolism Skin law.invention Mice chemistry.chemical_compound law recombinant adeno-associated viral vector genetics/metabolism Male Mice Mice Medicine genetics Adeno-associated virus Skin Lymphokines vascular endothelial growth factor Vascular Endothelial Growth Factors Genetic transfer Gene Transfer Techniques Gene Therapy Dependovirus Immunohistochemistry Vascular endothelial growth factor Recombinant DNA Intercellular Signaling Peptides and Proteins Burns burn injury metabolism/pathology metabolism/pathology Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Wound Healing Nitric Oxide Synthase Type III Genetic Vectors Enzyme-Linked Immunosorbent Assay Inbred C57BL Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Nitric Oxide Synthase nitric oxide Animals Burns metabolism/pathology/physiopathology/therapy Dependovirus Endothelial Growth Factors genetics/metabolism Enzyme-Linked Immunosorbent Assay Gene Therapy Gene Transfer Techniques Genetic Vectors Immunohistochemistry Intercellular Signaling Peptides and Proteins genetics/metabolism Lymphokines physiology beta-Galactosidase Animals gene therapy Wound Healing business.industry Genetic Therapy beta-Galactosidase metabolism/pathology/physiopathology/therapy Animals Burn genetics/metabolism Enzyme-Linked Immunosorbent Assay Gene Therapy Gene Transfer Techniques Genetic Vectors Immunohistochemistry Intercellular Signaling Peptides and Protein Mice Inbred C57BL Adenoviridae chemistry genetics/metabolism Lymphokine physiology Immunology Cancer research Nitric Oxide Synthase business Wound healing metabolism |
| Popis: | The purpose of this study was to investigate the effect of recombinant adeno-associated viral (rAAV) vector-mediated human vascular endothelial growth factor (VEGF165) transfer on experimental burn wounds.Randomized experiment.Research laboratory.C57BL/6 male mice weighing 25-30 g.Mice were immersed in 80 degrees C water for 10 secs to achieve a partial-thickness scald burn. Animals were randomized to receive at two injection sites on the edge of the burn either 1011 copies of the rAAV-VEGF165 or the vector carrying the control and inert gene beta-galactosidase (rAAV-LacZ). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of VEGF expression (immunohistochemistry) and VEGF wound content (enzyme-linked immunosorbent assay), determination of wound nitrite, and measurement of messenger RNA (mRNA) for endothelial and inducible nitric oxide synthase (eNOS and iNOS).rAAV-VEGF165 increased epithelial proliferation, angiogenesis, and maturation of the extracellular matrix. Furthermore, gene transfer enhanced VEGF expression, studied by immunohistochemistry, and the wound content of the mature protein (rAAV-LacZ, 11 +/- 5 pg/wound; rAAV-VEGF165, 104 +/- 7 pg/wound). Moreover, VEGF165 gene transfer increased wound content of nitrate. Finally, rAAV-VEGF165 administration enhanced the messenger RNA for eNOS (rAAV-VEGF165, 1.1 +/- 0.2 relative amount of eNOS mRNA; rAAV-LacZ, 0.66 +/- 0.3 relative amount of eNOS mRNA) and iNOS (rAAV-VEGF165, 0.8 +/- 0.09 relative amount of iNOS mRNA; rAAV-LacZ, 0.45 +/- 0.05 relative amount of iNOS mRNA).Our study suggests that rAAV-VEGF gene transfer may be an effective therapeutic approach to improve clinical outcomes after thermal injury. |
| Databáze: | OpenAIRE |
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