Abstract
Cardiovascular disease is a major cause of morbidity and mortality in contemporary societies. While progress in conventional treatment modalities is making steady and incremental gains to reduce this disease burden, there remains a need to explore new and potentially therapeutic approaches. Gene therapy, which was initially envisioned as a treatment strategy for inherited monogenic disorders, has been found to hold broader potential that also includes acquired polygenic diseases, such as atherosclerosis, arrhythmias, and heart failure. Advances in the understanding of the molecular basis of conditions such as these, together with the evolution of increasingly efficient gene transfer technology, have placed some cardiovascular pathophysiologies within the reach of gene-based therapy. In fact, gene therapy holds great promise as a targeted treatment for cardiovascular diseases. One of the major hurdles for effective cardiovascular gene therapy is the delivery of the viral vectors to the heart. In this chapter, we will present the various types of delivery techniques in preclinical, large animal models of cardiovascular diseases.
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References
Logeart, D., Hatem, S.N., Heimburger, M., Le Roux, A., Michel, J.B., Mercadier, J.J. (2001) How to optimize in vivo gene transfer to cardiac myocytes: mechanical or pharmacological procedures? Hum Gene Ther 12, 1601–1610.
Suzuki, G., Lee, T.C., Fallavollita, J.A., Canty, J.M, Jr. (2005) Adenoviral gene transfer of FGF-5 to hibernating myocardium improves function and stimulates myocytes to hypertrophy and reenter the cell cycle. Circ Res 96, 767–775.
Lai, N.C., Roth, D.M., Gao, M.H., et al. (2000) Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity. Circulation 102, 2396–2401.
Hayase, M., Del Monte, F., Kawase, Y., et al. (2005) Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade. Am J Physiol Heart Circ Physiol288, H2995–H3000.
Kaye, D.M., Preovolos, A., Marshall, T., et al. (2007) Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. J Am Coll Cardiol 50, 253–260.
Preovolos, A.C., Mennen, M.T., Bilney, A., Mariani, J., Kaye, D.M., Power, J.M. (2006) Development of a novel perfusion technique to allow targeted delivery of gene therapy – the V-Focus system. J Extra Corpor Technol 38, 51–52.
Raake, P.W., Hinkel, R., Muller, S., et al. (2008) Cardio-specific long-term gene expression in a porcine model after selective pressure-regulated retroinfusion of adeno-associated viral (AAV) vectors. Gene Ther 15, 12–17.
Raake, P., von Degenfeld, G., Hinkel, R., et al. (2004) Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: comparison with surgical and percutaneous intramyocardial gene delivery.J Am Coll Cardiol 44, 1124–1129.
Muller, O.J., Katus, H.A., Bekeredjian, R. (2007) Targeting the heart with gene therapy-optimized gene delivery methods. Cardiovasc Res 73, 453–462.
Smits, P.C., van Langenhove, G., Schaar, M., et al. (2002) Efficacy of percutaneous intra-myocardial injections using a nonfluoroscopic 3-D mapping based catheter system. Cardiovasc Drugs Ther 16, 527–533.
Kornowski, R., Leon, M.B., Fuchs, S., et al. (2000) Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models. J Am Coll Cardiol 35, 1031–1039.
Hoshino, K., Kimura, T., De Grand, A.M., Yoneyama, R., Kawase, Y., Houser, S., Ly, Q.H., Kushibiki, T., Kurukawa, Y., Ono, K., Tabata, Y., Frangioni, J.V., Kita, T., Hajjar, R.J., Hayase, M. (2006) Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres. Gene Ther 13, 1320–1327.
Anderl, J.N., Robey, T.E., Stayton, P.S., Murry, C.E. (2009) Retention and biodistribution of microspheres injected into ischemic myocardium. J Biomed Mater Res A 88, 704–710.
Grossman, P.M., Han, Z., Palasis, M., Barry, J.J., Lederman, R.J. (2002) Incomplete retention after direct myocardial injection. Catheter Cardiovasc Interv 55, 392–397.
Xiao, Y.F., Sigg, D.C., Ujhelyi, M.R., Wilhelm, J.J., Richardson, E.S., Iaizzo, P.A. (2008) Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias. Am J Physiol Heart Circ Physiol 294, H2212–H2218.
Vassalli, G., Bueler, H., Dudler, J., von Segesser, L.K., Kappenberger, L. (2003) Adeno-associated virus (AAV) vectors achieve prolonged transgene expression in mouse myocardium and arteries in vivo: a comparative study with adenovirus vectors. Int J Cardiol 90, 229–238.
Sosa, E., Scanavacca, M., d’Avila, A., Oliveira, F., Ramires, J.A. (2000) Nonsurgical transthoracic epicardial catheter ablation to treat recurrent ventricular tachycardia occurring late after myocardial infarction. J Am Coll Cardiol 35, 1442–1449.
Hou, D., March, K.L. (2003) A novel percutaneous technique for accessing the normal pericardium: a single-center successful experience of 53 porcine procedures. J Invasive Cardiol 15, 13–17.
d’Avila, A., Neuzil, P., Thiagalingam, A., et al. (2007) Experimental efficacy of pericardial instillation of anti-inflammatory agents during percutaneous epicardial catheter ablation to prevent postprocedure pericarditis. J Cardiovasc Electrophysiol 18, 1178–1783.
Weaver, M.E., Pantely, G.A., Bristow, J.D., Ladley, H.D. (1986) A quantitative study of the anatomy and distribution of coronary arteries in swine in comparison with other animals and man. Cardiovasc Res 20, 907–917.
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Kawase, Y., Ladage, D., Hajjar, R.J. (2011). Method of Gene Delivery in Large Animal Models of Cardiovascular Diseases. In: Duan, D. (eds) Muscle Gene Therapy. Methods in Molecular Biology, vol 709. Humana Press. https://doi.org/10.1007/978-1-61737-982-6_23
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DOI: https://doi.org/10.1007/978-1-61737-982-6_23
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