Abstract
Angiogenesis, vasculogenesis, and arteriogenesis are endogenous responses to obstructive arterial disease or trauma causing tissue ischemia such as atherosclerotic plaques obstructing perfusion of the lower limbs or myocardial ischemia. Sufficient growth of collateral vessels is often impaired in patients due to factors such as the underlying atherosclerosis, age, or diabetes. There are many preclinical and clinical studies seeking exogenous angiogenesis induction to alleviate tissue ischemia. Translation of these therapies into clinical applications could address a multitude of ailments including wound healing, tissue grafting, bone and muscle regeneration, and myocardial repair. Gene therapy approaches delivering angiogenic factors have been attempted using various gene delivery methods. This chapter will focus on evaluating preclinical studies investigating application of gene electrotransfer approaches for ischemic tissues, in particular for wound healing, peripheral artery disease, and myocardial infarction. Gene electrotransfer has been utilized to deliver proangiogenic factors such as vascular endothelial growth factor, insulin-like growth factor, basic fibroblast growth factor, angiopoietin, etc. Delivery and expression have been demonstrated minimally invasively and invasively to the skin, to skeletal muscle, and to cardiac muscle. Notable improvement in tissue perfusion was consistently reported in skin flap wound healing models, in hind limb ischemia models, and in cardiac muscle ischemia model.
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References
Ayuni EL, Gazdhar A, Giraud MN, Kadner A, Gugger M, Cecchini M et al (2010) In vivo electroporation mediated gene delivery to the beating heart. PLoS One 5:e14467
Basu G, Downey H, Guo S, Israel A, Asmar A, Hargrave B et al (2014) Prevention of distal flap necrosis in a rat random skin flap model by gene electro transfer delivering VEGF(165) plasmid. J Gene Med 16:55–65
Bulysheva AA, Hargrave B, Burcus N, Lundberg CG, Murray L, Heller R (2016) Vascular endothelial growth factor-A gene electrotransfer promotes angiogenesis in a porcine model of cardiac ischemia. Gene Ther 23:649–656
Collinson DJ, Donnelly R (2004) Therapeutic angiogenesis in peripheral arterial disease: can biotechnology produce an effective collateral circulation? Eur J Vasc Endovasc Surg 28:9–23
Eigeldinger-Berthou S, Buntschu P, Fluck M, Frobert A, Ferrie C, Carrel TP et al (2012) Electric pulses augment reporter gene expression in the beating heart. J Gene Med 14:191–203
Ferraro B, Cruz YL, Coppola D, Heller R (2009) Intradermal delivery of plasmid VEGF(165) by electroporation promotes wound healing. Mol Ther 17:651–657
Ferraro B, Cruz YL, Baldwin M, Coppola D, Heller R (2010) Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation. Gene Ther 17:763–769
Fujihara Y, Koyama H, Nishiyama N, Eguchi T, Takato T (2005) Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap. Br J Plast Surg 58:511–517
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB et al (2013) Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 127:e6–e245
Hargrave B, Downey H, Strange R Jr, Murray L, Cinnamond C, Lundberg C et al (2013) Electroporation-mediated gene transfer directly to the swine heart. Gene Ther 20:151–157
Hargrave B, Strange R Jr, Navare S, Stratton M, Burcus N, Murray L et al (2014) Gene electro transfer of plasmid encoding vascular endothelial growth factor for enhanced expression and perfusion in the ischemic Swine heart. PLoS One 9:e115235
Jiang J, Jiangl N, Gao W, Zhu J, Guo Y, Shen D et al (2006) Augmentation of revascularization and prevention of plasma leakage by angiopoietin-1 and vascular endothelial growth factor co-transfection in rats with experimental limb ischaemia. Acta Cardiol 61:145–153
Krumholz HM, Merrill AR, Schone EM, Schreiner GC, Chen J, Bradley EH et al (2009) Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality and readmission. Circ Cardiovasc Qual Outcomes 2:407–413
Makarevich P, Tsokolaeva Z, Shevelev A, Rybalkin I, Shevchenko E, Beloglazova I et al (2012) Combined transfer of human VEGF165 and HGF genes renders potent angiogenic effect in ischemic skeletal muscle. PLoS One 7:e38776
Marshall WG Jr, Boone BA, Burgos JD, Gografe SI, Baldwin MK, Danielson ML et al (2010) Electroporation-mediated delivery of a naked DNA plasmid expressing VEGF to the porcine heart enhances protein expression. Gene Ther 17:419–423
Mukherjee D, Bhatt DL, Roe MT, Patel V, Ellis SG (1999) Direct myocardial revascularization and angiogenesis--how many patients might be eligible? Am J Cardiol 84:598–600 A8
Nishikage S, Koyama H, Miyata T, Ishii S, Hamada H, Shigematsu H (2004) In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb. J Surg Res 120:37–46
Ouma GO, Rodriguez E, Muthumani K, Weiner DB, Wilensky RL, Mohler ER (2014) In vivo electroporation of constitutively expressed HIF-1alpha plasmid DNA improves neovascularization in a mouse model of limb ischemia. J Vasc Surg 59:786–793
Portlock JL, Keravala A, Bertoni C, Lee S, Rando TA, Calos MP (2006) Long-term increase in mVEGF164 in mouse hindlimb muscle mediated by phage phiC31 integrase after nonviral DNA delivery. Hum Gene Ther 17:871–876
Qian HS, Liu P, Huw LY, Orme A, Halks-Miller M, Hill SM et al (2006) Effective treatment of vascular endothelial growth factor refractory hindlimb ischemia by a mutant endothelial nitric oxide synthase gene. Gene Ther 13:1342–1350
Rabinovsky ED, Draghia-Akli R (2004) Insulin-like growth factor I plasmid therapy promotes in vivo angiogenesis. Mol Ther 9:46–55
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809
Sacramento CB, da Silva FH, Nardi NB, Yasumura EG, Baptista-Silva JC, Beutel A et al (2010) Synergistic effect of vascular endothelial growth factor and granulocyte colony-stimulating factor double gene therapy in mouse limb ischemia. J Gene Med 12:310–319
Steinstraesser L, Lam MC, Jacobsen F, Porporato PE, Chereddy KK, Becerikli M et al (2014) Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing. Mol Ther 22:734–742
Wolfram JA, Donahue JK (2013) Gene therapy to treat cardiovascular disease. J Am Heart Assoc 2:e000119
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Bulysheva, A.A., Heller, R. (2016). Gene Electrotransfer for Ischemic Tissue. In: Miklavcic, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-26779-1_58-1
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DOI: https://doi.org/10.1007/978-3-319-26779-1_58-1
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