Cotransfection of Vascular Endothelial Growth Factor-A and Platelet-Derived Growth Factor-B Via Recombinant Adeno-Associated Virus Resolves Chronic Ischemic Malperfusion
| Autor: | Andrea Fritz, Corinna Lebherz, Chiraz El-Aouni, Achim Pfosser, Christian Kupatt, Alexander Wuchrer, Eckart Thein, Andrea Banfi, Peter Boekstegers, Franziska Globisch, Michael Thormann, Jan Horstkotte, Rabea Hinkel |
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| Rok vydání: | 2010 |
| Předmět: |
Hibernating myocardium
medicine.medical_specialty Platelet-derived growth factor business.industry Angiogenesis viruses Growth factor medicine.medical_treatment Vascular endothelial growth factor Neovascularization Vascular endothelial growth factor A chemistry.chemical_compound Endocrinology chemistry Internal medicine Immunology Medicine Arteriogenesis medicine.symptom business Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of the American College of Cardiology. 56(5):414-422 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2010.03.050 |
| Popis: | Objectives We set out to investigate the ability of cardiotropic adeno-associated viral vector (AAV2.9 = recombinant adeno-associated virus [rAAV]) to induce prolonged expression of vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF)-B in a rabbit hindlimb ischemia model and a pig model of hibernating myocardium. Background Gene therapy to induce angiogenesis and arteriogenesis has produced mixed results. However, long-acting viruses, such as rAAV, as well as combined induction of angiogenesis and vessel maturation might extend the therapeutic potential. Methods In rabbits, 0.5 × 1011particles rAAV.VEGF-A with or without 1 × 1012particles rAAV.PDGF-B were retroinfused at day 7 after femoral artery excision. At days 7 and 35, collateral counts and perfusion were determined, each value given as the day 35/day 7 ratio. Capillary-to-muscle fiber ratio was determined at day 35. In pigs, implantation of a reduction stent graft into the circumflex artery led to complete occlusion at day 28. At this time point, retroinfusion of rAAV.VEGF-A (1 × 1013particles), rAAV.VEGF-A/PDGF-B (2 × 1012and 4 × 1012particles, respectively) or mock transfection was performed. Ejection fraction and left ventricular end-diastolic pressure were assessed at days 28 and 56. Results In rabbits, rAAV.VEGF-A strongly induced angiogenesis (capillary-to-muscle fiber ratio; 1.67 ± 0.09 vs. 1.32 ± 0.11 in rAAV.LacZ-treated limbs, p Conclusions Retroinfusion of rAAV.VEGF-A alone induces angiogenesis, but fails to enhance collateralization and perfusion, unless PDGF-B is cotransfected. In addition to neovascularization, rAAV.VEGF-A/PDGF-B improves regional and global myocardial function in hibernating myocardium. |
| Databáze: | OpenAIRE |
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