Arteriogenic therapy based on simultaneous delivery of VEGF-A and FGF4 genes improves the recovery from acute limb ischemia
| Autor: | Alicja Jozkowicz, Lorena Zentilin, Seppo Ylä-Herttuala, Mateusz Stoszko, Elisa Hytönen, Agnieszka Jazwa, Mateusz Tomczyk, Costanza Emanueli, Hevidar Taha, Jozef Dulak, Mauro Giacca |
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| Přispěvatelé: | A., Jazwa, M., Tomczyk, H. M., Taha, E., Hytonen, M., Stoszko, L., Zentilin, Giacca, Mauro, S., Yla Herttuala, C., Emanueli, A., Jozkowicz, J., Dulak |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Pathology
medicine.medical_specialty Computer Networks and Communications Angiogenesis Genetic enhancement viruses Femoral artery FGF4 030204 cardiovascular system & hematology Fibroblast growth factor Arteriogenesis VEGF-A 03 medical and health sciences angiogenesis 0302 clinical medicine Developmental Neuroscience medicine.artery Medicine 030304 developmental biology 0303 health sciences business.industry Research AAV Cell Biology Blood flow 3. Good health Neurology arteriogenesis business Ligation |
| Zdroj: | Vascular Cell |
| Popis: | Background: Gene therapy stimulating the growth of blood vessels is considered for the treatment of peripheral and myocardial ischemia. Here we aimed to achieve angiogenic synergism between vascular endothelial growth factor-A (VEGF-A, VEGF) and fibroblast growth factor 4 (FGF4) in murine normoperfused and ischemic limb muscles. Methods: Adeno-associated viral vectors (AAVs) carrying β-galactosidase gene (AAV-LacZ), VEGF-A (AAV-VEGF-A) or two angiogenic genes (AAV-FGF4-IRES-VEGF-A) were injected into the normo-perfused adductor muscles of C57Bl/6 mice. Moreover, in a different experiment, mice were subjected to unilateral hindlimb ischemia by femoral artery ligation followed by intramuscular injections of AAV-LacZ, AAV-VEGF-A or AAV-FGF4-IRES-VEGF-A below the site of ligation. Post-ischemic blood flow recovery was assessed sequentially by color laser Doppler. Mice were monitored for 28 days. Results: VEGF-A delivered alone (AAV-VEGF-A) or in combination with FGF4 (AAV-FGF4-IRES-VEGF-A) increased the number of capillaries in normo-perfused hindlimbs when compared to AAV-LacZ. Simultaneous overexpression of both agents (VEGF-A and FGF4) stimulated the capillary wall remodeling in the non-ischemic model. Moreover, AAV-FGF4-IRES-VEGF-A faster restored the post-ischemic foot blood flow and decreased the incidence of toe necrosis in comparison to AAV-LacZ. Conclusions: Synergy between VEGF-A and FGF4 to produce stable and functional blood vessels may be considered a promising option in cardiovascular gene therapy. |
| Databáze: | OpenAIRE |
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