Skip to main content

Advertisement

Log in

Advances in Gene-Based Therapy for Heart Failure

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Heart failure is a major cause of morbidity and mortality in western countries. While progress in current treatment modalities is making steady and incremental gains to reduce this disease burden, there remains a need to explore novel therapeutic strategies. Clinicians and researchers alike have thus looked towards novel adjunctive therapeutic strategies, including gene-based therapy for congestive heart failure (CHF). Advances in the understanding of the molecular basis of CHF, combined to the evolution of increasingly efficient gene transfer technology, have placed congestive heart failure within reach of gene-based therapy. This review will discuss issues related to gene vector systems, gene delivery strategies, and gene targets for intervention in the setting of CHF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

References

  1. Fuster, V., Badimon, L., Badimon, J. J., & Chesebro, J. H. (1992). The pathogenesis of coronary artery disease and the acute coronary syndromes (1). New England Journal of Medicine, 326, 242–250.

    PubMed  CAS  Google Scholar 

  2. Jessup, M., & Brozena, S. (2003). Heart failure. New England Journal of Medicine, 348, 2007–2018.

    PubMed  Google Scholar 

  3. Rosamond, W., Flegal, K., Furie, K., Go, A., Greenlund, K., Haase, N., et al. (2008). Heart disease and stroke statistics–2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 117, e25–e146.

    PubMed  Google Scholar 

  4. Landmesser, U., & Drexler, H. (2005). Chronic heart failure: an overview of conventional treatment versus novel approaches. Natural Clinical Practice in Cardiovascular Medicine, 2, 628–638.

    CAS  Google Scholar 

  5. Pislaru, S. V., & Simari, R. D. (2005). Gene transfer for ischemic cardiovascular disease: is this the end of the beginning or the beginning of the end? Natural Clinical Practice in Cardiovascular Medicine, 2, 138–144.

    CAS  Google Scholar 

  6. Ly, H., Kawase, Y., Yoneyama, R., & Hajjar, R. J. (2007). Gene Therapyapy in the treatment of heart failure. Physiology (Bethesda), 22, 81–96.

    CAS  Google Scholar 

  7. Isner, J. M. (2002). Myocardial Gene Therapyapy. Nature, 415, 234–239.

    PubMed  CAS  Google Scholar 

  8. Hajjar, R. J., del Monte, F., Matsui, T., & Rosenzweig, A. (2000). Prospects for Gene Therapyapy for heart failure. Circulation Research, 86, 616–621.

    PubMed  CAS  Google Scholar 

  9. Clackson, T. (2000). Regulated gene expression systems. Gene Therapyapy, 7, 120–125.

    CAS  Google Scholar 

  10. Pap, T., Gay, R. E., & Gay, S. (2000). Gene transfer: from concept to therapy. Current Opinion in Rheumatology, 12, 205–210.

    PubMed  CAS  Google Scholar 

  11. Hart, I. R. (1996). Tissue specific promoters in targeting systemically delivered Gene Therapyapy. Seminars in Oncology, 23, 154–158.

    PubMed  CAS  Google Scholar 

  12. Nettelbeck, D. M., Jerome, V., & Muller, R. (2000). Gene Therapyapy: designer promoters for tumour targeting. Trends in Genetics, 16, 174–181.

    PubMed  CAS  Google Scholar 

  13. Nishikawa, M., & Huang, L. (2001). Nonviral vectors in the new millennium: delivery barriers in gene transfer. Human Gene Therapyapy, 12, 861–870.

    CAS  Google Scholar 

  14. Kay, M. A., Glorioso, J. C., & Naldini, L. (2001). Viral vectors for Gene Therapyapy: the art of turning infectious agents into vehicles of therapeutics. Natural Medicines, 7, 33–40.

    CAS  Google Scholar 

  15. Felgner, P. L. (1997). Nonviral strategies for Gene Therapyapy. Scientific American, 276, 102–106.

    Article  PubMed  CAS  Google Scholar 

  16. Kawaguchi, H., Shin, W. S., Wang, Y., Inukai, M., Kato, M., Matsuo-Okai, Y., et al. (1997). In vivo gene transfection of human endothelial cell nitric oxide synthase in cardiomyocytes causes apoptosis-like cell death. Identification using Sendai virus-coated liposomes. Circulation, 95, 2441–2447.

    PubMed  CAS  Google Scholar 

  17. Qin, X. Q., Tao, N., Dergay, A., Moy, P., Fawell, S., Davis, A., et al. (1998). Interferon-beta Gene Therapyapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 95, 14411–14416.

    PubMed  CAS  Google Scholar 

  18. Nabel, E. G. (1995). Gene Therapyapy for cardiovascular disease. Circulation, 91, 541–548.

    PubMed  CAS  Google Scholar 

  19. Nabel, E. G., Simari, R., Yang, Z., San, H., & Nabel, G. J. (1997). In vivo gene transfer: a biological tool. Annals of the New York Academy of Sciences, 811, 289–292.

    PubMed  CAS  Google Scholar 

  20. Nabel, G. J. (2004). Genetic, cellular and immune approaches to disease therapy: past and future. Natural Medicines, 10, 135–141.

    CAS  Google Scholar 

  21. Nabel, G. J. (2003). The future of Gene Therapyapy. Ernst Schering Research Foundation Workshop:1–16.

  22. Isner, J. M. (2002). Myocardial Gene Therapy. Nature, 415, 234–239.

    PubMed  CAS  Google Scholar 

  23. Santiago, F. S., & Khachigian, L. M. (2001). Nucleic acid based strategies as potential therapeutic tools: mechanistic considerations and implications to restenosis. Journal of Molecular Medicine, 79, 695–706.

    PubMed  CAS  Google Scholar 

  24. Guzman, R. J., Lemarchand, P., Crystal, R. G., Epstein, S. E., & Finkel, T. (1993). Efficient and selective adenovirus-mediated gene transfer into vascular neointima. Circulation, 88, 2838–2848.

    PubMed  CAS  Google Scholar 

  25. Barr, E., Carroll, J., Kalynych, A. M., Tripathy, S. K., Kozarsky, K., Wilson, J. M., et al. (1994). Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Therapy, 1, 51–58.

    PubMed  CAS  Google Scholar 

  26. Communal, C., Huq, F., Lebeche, D., Mestel, C., Gwathmey, J. K., & Hajjar, R. J. (2003). Decreased efficiency of adenovirus-mediated gene transfer in aging cardiomyocytes. Circulation, 107, 1170–1175.

    PubMed  Google Scholar 

  27. Alba, R., Bosch, A., & Chillon, M. (2005). Gutless adenovirus: last-generation adenovirus for Gene Therapyapy. Gene Therapy, 12(1), S18–S27.

    PubMed  CAS  Google Scholar 

  28. Staba, M. J., Wickham, T. J., Kovesdi, I., & Hallahan, D. E. (2000). Modifications of the fiber in adenovirus vectors increase tropism for malignant glioma models. Cancer Gene Therapy, 7, 13–19.

    PubMed  CAS  Google Scholar 

  29. Zhou, Y. Y., Lakatta, E. G., & Xiao, R. P. (1998). Age-associated alterations in calcium current and its modulation in cardiac myocytes. Drugs & Aging, 13, 159–171.

    CAS  Google Scholar 

  30. Xiao, X., Li, J., McCown, T. J., & Samulski, R. J. (1997). Gene transfer by adeno-associated virus vectors into the central nervous system. Experimental Neurology, 144, 113–124.

    PubMed  CAS  Google Scholar 

  31. Xiao, X., McCown, T. J., Li, J., Breese, G. R., Morrow, A. L., & Samulski, R. J. (1997). Adeno-associated virus (AAV) vector antisense gene transfer in vivo decreases GABA(A) alpha1 containing receptors and increases inferior collicular seizure sensitivity. Brain Research, 756, 76–83.

    PubMed  CAS  Google Scholar 

  32. Yang, C. C., Xiao, X., Zhu, X., Ansardi, D. C., Epstein, N. D., Frey, M. R., et al. (1997). Cellular recombination pathways and viral terminal repeat hairpin structures are sufficient for adeno-associated virus integration in vivo and in vitro. Journal of Virology, 71, 9231–9247.

    PubMed  CAS  Google Scholar 

  33. Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J., et al. (2006). Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Natural Medicines, 12, 342–347.

    CAS  Google Scholar 

  34. Wu, Z., Asokan, A., & Samulski, R. J. (2006). Adeno-associated virus serotypes: vector toolkit for human Gene Therapyapy. Molecular Therapy, 14, 316–327.

    PubMed  CAS  Google Scholar 

  35. Inagaki, K., Fuess, S., Storm, T. A., Gibson, G. A., McTiernan, C. F., Kay, M. A., et al. (2006). Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. Molecular Therapy, 14, 45–53.

    PubMed  CAS  Google Scholar 

  36. Pacak, C. A., Mah, C. S., Thattaliyath, B. D., Conlon, T. J., Lewis, M. A., Cloutier, D. E., et al. (2006). Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circulation Research, 99, e3–e9.

    PubMed  CAS  Google Scholar 

  37. Zhu, T., Zhou, L., Mori, S., Wang, Z., McTiernan, C. F., Qiao, C., et al. (2005). Sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer. Circulation, 112, 2650–2659.

    PubMed  CAS  Google Scholar 

  38. Wang, Z., Zhu, T., Qiao, C., Zhou, L., Wang, B., Zhang, J., et al. (2005). Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nature Biotechnology, 23, 321–328.

    PubMed  CAS  Google Scholar 

  39. Weitzman, M. D., & Thistlethwaite, P. A. (2005). Breaking the barriers to global gene delivery. Nature Biotechnology, 23, 305–306.

    PubMed  CAS  Google Scholar 

  40. Monahan, P. E., & Samulski, R. J. (2000). AAV vectors: is clinical success on the horizon? Gene Therapy, 7, 24–30.

    PubMed  CAS  Google Scholar 

  41. Choi, V. W., Samulski, R. J., & McCarty, D. M. (2005). Effects of adeno-associated virus DNA hairpin structure on recombination. Journal of Virology, 79, 6801–6807.

    PubMed  CAS  Google Scholar 

  42. Fu, H., Muenzer, J., Samulski, R. J., Breese, G., Sifford, J., Zeng, X., et al. (2003). Self-complementary adeno-associated virus serotype 2 vector: global distribution and broad dispersion of AAV-mediated transgene expression in mouse brain. Molecular Therapy, 8, 911–917.

    PubMed  CAS  Google Scholar 

  43. McCarty, D. M., Fu, H., Monahan, P. E., Toulson, C. E., Naik, P., & Samulski, R. J. (2003). Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Therapy, 10, 2112–2118.

    PubMed  CAS  Google Scholar 

  44. Cavazzana-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., et al. (2000). Gene Therapyapy of human severe combined immunodeficiency (SCID)-X1 disease. Science, 288, 669–672.

    PubMed  CAS  Google Scholar 

  45. Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P., et al. (2003). LMO2-associated clonal T cell proliferation in two patients after Gene Therapyapy for SCID-X1. Science, 302, 415–419.

    PubMed  CAS  Google Scholar 

  46. Higuchi, K., & Medin, J. A. (2007). Lentiviral vectors for Gene Therapyapy of heart disease. Journal of Cardiology, 49, 1–11.

    PubMed  Google Scholar 

  47. Naldini, L., Blomer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., et al. (1996). In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science, 272, 263–267.

    PubMed  CAS  Google Scholar 

  48. Klages, N., Zufferey, R., & Trono, D. (2000). A stable system for the high-titer production of multiply attenuated lentiviral vectors. Molecular Therapy, 2, 170–176.

    PubMed  CAS  Google Scholar 

  49. Sirven, A., Pflumio, F., Zennou, V., Titeux, M., Vainchenker, W., Coulombel, L., et al. (2000). The human immunodeficiency virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells. Blood, 96, 4103–4110.

    PubMed  CAS  Google Scholar 

  50. Bonci, D., Cittadini, A., Latronico, M. V., Borello, U., Aycock, J. K., Drusco, A., et al. (2003). ‘‘Advanced’’ generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo. Gene Therapy, 10, 630–636.

    PubMed  CAS  Google Scholar 

  51. Galimi, F., Noll, M., Kanazawa, Y., Lax, T., Chen, C., Grompe, M., et al. (2002). Gene Therapyapy of Fanconi anemia: preclinical efficacy using lentiviral vectors. Blood, 100, 2732–2736.

    PubMed  CAS  Google Scholar 

  52. Galimi, F., & Verma, I. M. (2002). Opportunities for the use of lentiviral vectors in human Gene Therapyapy. Current Topics in Microbiology and Immunology, 261, 245–254.

    PubMed  CAS  Google Scholar 

  53. Phillips, M. I., Tang, Y., Schmidt-Ott, K., Qian, K., & Kagiyama, S. (2002). Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. Hypertension, 39, 651–655.

    PubMed  CAS  Google Scholar 

  54. Fromes, Y., Salmon, A., Wang, X., Collin, H., Rouche, A., Hagege, A., et al. (1999). Gene delivery to the myocardium by intrapericardial injection. Gene Therapy, 6, 683–688.

    PubMed  CAS  Google Scholar 

  55. Guzman, R. J., Lemarchand, P., Crystal, R. G., Epstein, S. E., & Finkel, T. (1993). Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circulation Research, 73, 1202–1207.

    PubMed  CAS  Google Scholar 

  56. Markkanen, J. E., Rissanen, T. T., Kivela, A., & Yla-Herttuala, S. (2005). Growth factor-induced therapeutic angiogenesis and arteriogenesis in the heart–Gene Therapyapy. Cardiovascular Research, 65, 656–664.

    PubMed  CAS  Google Scholar 

  57. Koransky, M. L., Robbins, R. C., & Blau, H. M. (2002). VEGF gene delivery for treatment of ischemic cardiovascular disease. Trends in Cardiovascular Medicine, 12, 108–114.

    PubMed  CAS  Google Scholar 

  58. Naimark, W. A., Lepore, J. J., Klugherz, B. D., Wang, Z., Guy, T. S., Osman, H., et al. (2003). Adenovirus-catheter compatibility increases gene expression after delivery to porcine myocardium. Human Gene Therapy, 14, 161–166.

    PubMed  CAS  Google Scholar 

  59. Losordo, D. W., Vale, P. R., Hendel, R. C., Milliken, C. E., Fortuin, F. D., Cummings, N., et al. (2002). Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation, 105, 2012–2018.

    PubMed  CAS  Google Scholar 

  60. Isner, J. M., Vale, P. R., Symes, J. F., & Losordo, D. W. (2001). Assessment of risks associated with cardiovascular Gene Therapyapy in human subjects. Circulation Research, 89, 389–400.

    PubMed  CAS  Google Scholar 

  61. Lathi, K. G., Vale, P. R., Losordo, D. W., Cespedes, R. M., Symes, J. F., Esakof, D. D., et al. (2001). Gene Therapyapy with vascular endothelial growth factor for inoperable coronary artery disease: anesthetic management and results. Anesthesia and Analgesia, 92, 19–25.

    PubMed  CAS  Google Scholar 

  62. Vale, P. R., Losordo, D. W., Milliken, C. E., McDonald, M. C., Gravelin, L. M., Curry, C. M., et al. (2001). Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation, 103, 2138–2143.

    PubMed  CAS  Google Scholar 

  63. Hajjar, R. J., Schmidt, U., Matsui, T., Guerrero, J. L., Lee, K. H., Gwathmey, J. K., et al. (1998). Modulation of ventricular function through gene transfer in vivo. Proceedings of the National Academy of Sciences of the United States of America, 95, 5251–5256.

    PubMed  CAS  Google Scholar 

  64. Beeri, R., Guerrero, J. L., Supple, G., Sullivan, S., Levine, R. A., & Hajjar, R. J. (2002). New efficient catheter-based system for myocardial gene delivery. Circulation, 106, 1756–1759.

    PubMed  CAS  Google Scholar 

  65. Nagata, K., Marban, E., Lawrence, J. H., & Donahue, J. K. (2001). Phosphodiesterase inhibitor-mediated potentiation of adenovirus delivery to myocardium. Journal of Molecular and Cellular Cardiology, 33, 575–580.

    PubMed  CAS  Google Scholar 

  66. 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? Human Gene Therapy, 12, 1601–1610.

    PubMed  CAS  Google Scholar 

  67. Boekstegers, P., von Degenfeld, G., Giehrl, W., Heinrich, D., Hullin, R., et al. (2000). Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins. Gene Therapy, 7, 232–240.

    PubMed  CAS  Google Scholar 

  68. Hayase, M., Del Monte, F., Kawase, Y., Macneill, B. D., McGregor, J., Yoneyama, R., et al. (2005). Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade. American Journal of Physiology. Heart and Circulatory Physiology, 288, H2995–H3000.

    PubMed  CAS  Google Scholar 

  69. Prevolos, A., Mennen, M., Bilney, A., Mariani, J., Kaye, D., & Power, J. (2006). developpement of a novel perfusion technique to allow targeted delivery of Gene Therapyapy– the V-Focus system. Journal of Extra-corporeal Technology, 38, 51–52.

    Google Scholar 

  70. Kaye, D. M., Preovolos, A., Marshall, T., Byrne, M., Hoshijima, M., Hajjar, R., et al. (2007). Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. Journal of the American College of Cardiology, 50, 253–260.

    PubMed  CAS  Google Scholar 

  71. Rockman, H. A., Koch, W. J., & Lefkowitz, R. J. (2002). Seven-transmembrane-spanning receptors and heart function. Nature, 415, 206–212.

    PubMed  CAS  Google Scholar 

  72. Pleger, S. T., Boucher, M., Most, P., & Koch, W. J. (2007). Targeting myocardial beta-adrenergic receptor signaling and calcium cycling for heart failure Gene Therapyapy. Journal of Cardiac Failure, 13, 401–414.

    PubMed  CAS  Google Scholar 

  73. Morissette, M. R., & Rosenzweig, A. (2005). Targeting survival signaling in heart failure. Current Opinion in Pharmacology, 5, 165–170.

    PubMed  CAS  Google Scholar 

  74. Prestle, J., Quinn, F. R., & Smith, G. L. (2003). Ca(2+)-handling proteins and heart failure: novel molecular targets? Current Medicinal Chemistry, 10, 967–981.

    PubMed  CAS  Google Scholar 

  75. Carr, A. N., Schmidt, A. G., Suzuki, Y., del Monte, F., Sato, Y., et al. (2002). Type 1 phosphatase, a negative regulator of cardiac function. Molecular and Cellular Biology, 22, 4124–4135.

    PubMed  CAS  Google Scholar 

  76. El-Armouche, A., Pamminger, T., Ditz, D., Zolk, O., & Eschenhagen, T. (2004). Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts. Cardiovascular Research, 61, 87–93.

    PubMed  CAS  Google Scholar 

  77. Braz, J. C., Gregory, K., Pathak, A., Zhao, W., Sahin, B., Klevitsky, R., et al. (2004). PKC-alpha regulates cardiac contractility and propensity toward heart failure. Natural Medicines, 10, 248–254.

    CAS  Google Scholar 

  78. Kranias, E. G., & Bers, D. M. (2007). Calcium and cardiomyopathies. Sub-cellular Biochemistry, 45, 523–537.

    Article  PubMed  CAS  Google Scholar 

  79. del Monte, F., & Hajjar, R. J. (2003). Targeting calcium cycling proteins in heart failure through gene transfer. Journal of Physiology, 546, 49–61.

    PubMed  Google Scholar 

  80. Hoshijima, M., Ikeda, Y., Iwanaga, Y., Minamisawa, S., Date, M. O., Gu, Y., et al. (2002). Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Natural Medicines, 8, 864–871.

    CAS  Google Scholar 

  81. Iwanaga, Y., Hoshijima, M., Gu, Y., Iwatate, M., Dieterle, T., Ikeda, Y., et al. (2004). Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. Journal of Clinical Investigation, 113, 727–736.

    PubMed  CAS  Google Scholar 

  82. del Monte, F., Harding, S. E., Dec, G. W., Gwathmey, J. K., & Hajjar, R. J. (2002). Targeting phospholamban by gene transfer in human heart failure. Circulation, 105, 904–907.

    PubMed  Google Scholar 

  83. Ziolo, M. T., Martin, J. L., Bossuyt, J., Bers, D. M., & Pogwizd, S. M. (2005). Adenoviral gene transfer of mutant phospholamban rescues contractile dysfunction in failing rabbit myocytes with relatively preserved SERCA function. Circulation Research, 96, 815–817.

    PubMed  CAS  Google Scholar 

  84. Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U., et al. (2003). Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science, 299, 1410–1413.

    PubMed  CAS  Google Scholar 

  85. Haghighi, K., Kolokathis, F., Gramolini, A. O., Waggoner, J. R., Pater, L., Lynch, R. A., et al. (2006). A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America, 103, 1388–1393.

    PubMed  CAS  Google Scholar 

  86. Pathak, A., del Monte, F., Zhao, W., Schultz, J. E., Lorenz, J. N., Bodi, I., et al. (2005). Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1. Circulation Research, 96, 756–766.

    PubMed  CAS  Google Scholar 

  87. Most, P., Pleger, S. T., Volkers, M., Heidt, B., Boerries, M., Weichenhan, D., et al. (2004). Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. Journal of Clinical Investigation, 114, 1550–1563.

    PubMed  CAS  Google Scholar 

  88. Dally, S., Bredoux, R., Corvazier, E., Andersen, J. P., Clausen, J. D., Dode, L., et al. (2006). Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c). Biochemical Journal, 395, 249–258.

    PubMed  CAS  Google Scholar 

  89. Lipskaia, L., & Lompre, A. M. (2004). Alteration in temporal kinetics of Ca2+ signaling and control of growth and proliferation. Biology of the Cell, 96, 55–68.

    PubMed  CAS  Google Scholar 

  90. Movsesian, M. A., Karimi, M., Green, K., & Jones, L. R. (1994). Ca(2+)-transporting ATPase, phospholamban, and calsequestrin levels in nonfailing and failing human myocardium. Circulation, 90, 653–657.

    PubMed  CAS  Google Scholar 

  91. Schwinger, R. H., Bohm, M., Schmidt, U., Karczewski, P., Bavendiek, U., Flesch, M., et al. (1995). Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation, 92, 3220–3228.

    PubMed  CAS  Google Scholar 

  92. Hasenfuss, G., Reinecke, H., Studer, R., Meyer, M., Pieske, B., Holtz, J., et al. (1994). Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circulation Research, 75, 434–442.

    PubMed  CAS  Google Scholar 

  93. Arai, M., Alpert, N. R., MacLennan, D. H., Barton, P., & Periasamy, M. (1993). Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. Circulation Research, 72, 463–469.

    PubMed  CAS  Google Scholar 

  94. de la Bastie, D., Levitsky, D., Rappaport, L., Mercadier, J. J., Marotte, F., Wisnewsky, C., et al. (1990). Function of the sarcoplasmic reticulum and expression of its Ca2(+)-ATPase gene in pressure overload-induced cardiac hypertrophy in the rat. Circulation Research, 66, 554–564.

    PubMed  Google Scholar 

  95. Mercadier, J. J., Lompre, A. M., Duc, P., Boheler, K. R., Fraysse, J. B., Wisnewsky, C., et al. (1990). Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. Journal of Clinical Investigation, 85, 305–309.

    PubMed  CAS  Google Scholar 

  96. Miyamoto, M. I., del Monte, F., Schmidt, U., DiSalvo, T. S., Kang, Z. B., et al. (2000). Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proceedings of the National Academy of Sciences of the United States of America, 97, 793–798.

    PubMed  CAS  Google Scholar 

  97. Davia, K., Bernobich, E., Ranu, H. K., del Monte, F., Terracciano, C. M., MacLeod, K. T., et al. (2001). SERCA2A overexpression decreases the incidence of aftercontractions in adult rabbit ventricular myocytes. Journal of Molecular and Cellular Cardiology, 33, 1005–1015.

    PubMed  CAS  Google Scholar 

  98. Trost, S. U., Belke, D. D., Bluhm, W. F., Meyer, M., Swanson, E., & Dillmann, W. H. (2002). Overexpression of the sarcoplasmic reticulum Ca(2+)-ATPase improves myocardial contractility in diabetic cardiomyopathy. Diabetes, 51, 1166–1171.

    PubMed  CAS  Google Scholar 

  99. Ito, K., Yan, X., Feng, X., Manning, W. J., Dillmann, W. H., & Lorell, B. H. (2001). Transgenic expression of sarcoplasmic reticulum Ca(2+) atpase modifies the transition from hypertrophy to early heart failure. Circulation Research, 89, 422–429.

    PubMed  CAS  Google Scholar 

  100. Nakayama, H., Otsu, K., Yamaguchi, O., Nishida, K., Date, M. O., Hongo, K., et al. (2003). Cardiac-specific overexpression of a high Ca2+ affinity mutant of SERCA2a attenuates in vivo pressure overload cardiac hypertrophy. FASEB Journal, 17, 61–63.

    PubMed  CAS  Google Scholar 

  101. Muller, O. J., Lange, M., Rattunde, H., Lorenzen, H. P., Muller, M., Frey, N., et al. (2003). Transgenic rat hearts overexpressing SERCA2a show improved contractility under baseline conditions and pressure overload. Cardiovascular Research, 59, 380–389.

    PubMed  CAS  Google Scholar 

  102. Lipskaia, L., del Monte, F., Capiod, T., Yacoubi, S., Hadri, L., Hours, M., et al. (2005). Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat. Circulation Research, 97, 488–495.

    PubMed  CAS  Google Scholar 

  103. del Monte, F., Williams, E., Lebeche, D., Schmidt, U., Rosenzweig, A., Gwathmey, J. K., et al. (2001). Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure. Circulation, 104, 1424–1429.

    PubMed  Google Scholar 

  104. Terracciano, C. (2002). Functional consequences of Na/Ca exchanger overexpression in cardiac myocytes. Annals of the New York Academy of Sciences, 976, 520–527.

    Article  PubMed  CAS  Google Scholar 

  105. del Monte, F., Lebeche, D., Guerrero, J. L., Tsuji, T., Doye, A. A., Gwathmey, J. K., et al. (2004). Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling. Proceedings of the National Academy of Sciences of the United States of America, 101, 5622–5627.

    PubMed  Google Scholar 

  106. del Monte, F., Harding, S. E., Schmidt, U., Matsui, T., Kang, Z. B., Dec, G. W., et al. (1999). Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a. Circulation, 100, 2308–2311.

    Google Scholar 

  107. Sakata, S., Lebeche, D., Sakata, N., Sakata, Y., Chemaly, E. R., Liang, L. F., et al. (2007). Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins. Journal of Molecular and Cellular Cardiology, 42, 852–861.

    PubMed  CAS  Google Scholar 

  108. Sakata, S., Lebeche, D., Sakata, Y., Sakata, N., Chemaly, E. R., Liang, L. F., et al. (2006). Mechanical and metabolic rescue in a type II diabetes model of cardiomyopathy by targeted gene transfer. Molecular Therapy, 13, 987–996.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roger J. Hajjar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ly, H.Q., Kawase, Y. & Hajjar, R.J. Advances in Gene-Based Therapy for Heart Failure. J. of Cardiovasc. Trans. Res. 1, 127–136 (2008). https://doi.org/10.1007/s12265-008-9022-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-008-9022-4

Keywords

Navigation