Long-term VEGF-A expression promotes aberrant angiogenesis and fibrosis in skeletal muscle
| Autor: | E Pasanen, Tuomas T. Rissanen, Henna Karvinen, Seppo Ylä-Herttuala, Mauro Giacca, Petra Korpisalo, Elisa Vähäkangas, Agnieszka Jazwa |
|---|---|
| Přispěvatelé: | H., Karvinen, E., Pasanen, T. T., Rissanen, P., Korpisalo, E., Vähäkanga, A., Jazwa, Giacca, Mauro, S., Ylä Herttuala |
| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
CD31 Angiogenesis viruses 030204 cardiovascular system & hematology VEGF-A Neovascularization 0302 clinical medicine Ischemia Fibrosis blood supply/pathology Neovascularization 0303 health sciences AAV Gene Therapy Skeletal Dependovirus therapy Muscle adverse effects/genetics Cell biology blood supply/pathology Vascular endothelial growth factor A medicine.anatomical_structure Muscle Molecular Medicine Rabbits medicine.symptom ITGA7 adverse effects/methods Humans Ischemia Animals Dependovirus Fibrosi etiology Neovascularization Physiologic genetics Rabbits Vascular Endothelial Growth Factor A Biology Gene delivery 03 medical and health sciences Genetics medicine Animals Humans Muscle Skeletal Physiologic Molecular Biology 030304 developmental biology Animals Dependovirus Fibrosis etiology Follow-Up Studies Gene Therapy therapy adverse effects/methods fibrosis angiogenesi Skeletal muscle Genetic Therapy medicine.disease Molecular biology Follow-Up Studies |
| Zdroj: | Gene Therapy |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | Vascular endothelial growth factor A (VEGF-A) induces strong angiogenesis and it has been widely used in proangiogenic gene therapy studies. However, little is known about long-term effects of VEGF-A expression in skeletal muscle. Here the long- term effects of adeno-associated virus (AAV) encoding human VEGF-A(165) (AAV-VEGF-A) gene transfer in normal and ischemic rabbit hindlimb skeletal muscles were studied. AAV-LacZ was used as a control. In one-year follow-up, a remarkable increase in skeletal muscle perfusion compared with AAV-LacZ was observed measured with Doppler and contrast pulse sequence ultrasound. Angiogenesis was also seen in histology as enlarged and sprouting capillaries. In addition to favorable angiogenic effects, aberrant vascular structures with CD31 positive cell layers were seen inside muscle fibers after AAV-VEGF-A gene transfer. Importantly, we found increased amounts of extracellular matrix with a high number of macrophages and fibrosis in AAV-VEGF-A transduced muscles. No changes in skeletal muscle morphology were detected in AAV-LacZ transduced muscles. Our results indicate that local AAV-VEGF-A gene transfer efficiently promotes long-term angiogenesis in large animal model. However, non-regulated expression of VEGF-A causes unfavorable changes in muscle morphology, which suggests the need for regulation of the transgene expression in long-term AAV-mediated VEGF-A gene transfer applications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|