Cotransfection of vascular endothelial growth factor-A and platelet-derived growth factor-B via recombinant adeno-associated virus resolves chronic ischemic malperfusion role of vessel maturation

Journal of the American College of Cardiology
C KupattP Boekstegers

Abstract

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. 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. In rabbits, 0.5 x 10(11) particles rAAV.VEGF-A with or without 1 x 10(12) particles 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 x 10(13) particles), rAAV.VEGF-A/PDGF-B (2 x 10(12) and 4 x 10(12) particles, respectively) or mock transfection was performed. Ejection fraction and left ventricular end-diastolic press...Continue Reading

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Citations

Feb 10, 2012·Cardiovascular Research·Rabea HinkelChristian Kupatt
Jan 5, 2013·Circulation Research·Betty DescampsCostanza Emanueli
Jun 10, 2014·Nature Communications·Rabea HinkelChristian Kupatt
Sep 27, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Wen-Wu BaiYu-Xia Zhao
Mar 26, 2011·Expert Opinion on Biological Therapy·Rabea HinkelChristian Kupatt
Feb 6, 2015·Expert Opinion on Biological Therapy·Teresa TrenkwalderRabea Hinkel
Jan 22, 2015·Expert Opinion on Biological Therapy·Dario BongiovanniChristian Kupatt
Nov 23, 2011·Biochemical Society Transactions·Silvia ReginatoAndrea Banfi
Sep 14, 2016·Vascular Pharmacology·Agnieszka JazwaJozef Dulak
Feb 9, 2017·Current Opinion in Cardiology·Kyle ChamberlainThomas Weber
Jan 14, 2017·Journal of the American College of Cardiology·Rabea HinkelChristian Kupatt
Jan 1, 2012·Cells·Ludovic MellyAnna Marsano
Nov 3, 2017·Cell Adhesion & Migration·Hongyu ZhuYue Tong
Nov 17, 2012·Journal of Vascular Research·Somiraa S SaidKibret Mequanint
Feb 24, 2015·World Journal of Experimental Medicine·Edith Renaud-GabardosAnne-Catherine Prats
Jun 1, 2018·Human Gene Therapy·Tilman ZieglerChristian Kupatt
Oct 2, 2013·Journal of the American Heart Association·Kory J LavineDouglas L Mann
Feb 14, 2014·EMBO Molecular Medicine·Christian Kupatt, Rabea Hinkel
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Jan 11, 2020·Stem Cells Translational Medicine·Roberto Gianni-BarreraAndrea Banfi
Oct 26, 2018·Circulation Research·Kiyotake IshikawaRoger J Hajjar
Mar 23, 2011·Journal of Cellular and Molecular Medicine·Thomas WolffAndrea Banfi
Mar 10, 2017·Expert Opinion on Biological Therapy·Kay MaedaMarc Ruel
Oct 3, 2020·Biomolecules·Andreas SpannbauerMariann Gyöngyösi
Jan 8, 2021·Biomaterials·Raquel C GonçalvesJoão F Mano
Mar 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Beate RieblingerBenjamin Schusser

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