Skip to main content

Gene Therapy: Role in Myocardial Protection

  • Chapter
The Vascular Endothelium II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 176/II))

Abstract

Heart failure associated with coronary artery disease is a major cause of morbidity and mortality. Recent developments in the understanding of the molecular mechanisms of heart failure have led to the identification of novel therapeutic targets which, combined with the availability of efficient gene delivery vectors, offer the opportunity for the design of gene therapies for protection of the myocardium. Viral-based therapies have been developed to treat polygenic and complex diseases such as myocardial ischaemia, hypertension, atherosclerosis and restenosis. Some of these experimental therapies are now undergoing clinical evaluation in patients with cardiovascular diseases. In this review we will focus on the latest advances in the field of gene therapy for treatment of heart failure and their clinical application.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Antos CL, McKinsey TA, Frey N, Kutschke W, McAnally J, Shelton J, Richardson JA, Hill JA, Olson EN (2002) Activated glycogen synthase kinase 3-β suppresses cardiac hypertrophy in vivo. Proc Natl Acad Sci USA 99:907–912

    Article  PubMed  CAS  Google Scholar 

  • Asahara T, Bauters C, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM (1995) Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 92:II365–II371

    PubMed  CAS  Google Scholar 

  • Asakura M, Kitakaze M, Taskashima S, Liao Y, Ishikura F, Yoshinaka T, Ohmoto H, Node K, Yoshino K, Ishiguro H, Asanuma H, Sanada S, Matsumara Y, Takeda H, Beppu S, Tada M, Hori M, Higashiyama S (2002) Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat Med 8:35–40

    Article  PubMed  CAS  Google Scholar 

  • Carden DL, Granger DN (2000) Pathophysiology of ischemia-reperfusion injury. Am J Pathol 190:255–266

    Article  CAS  Google Scholar 

  • Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395

    Article  PubMed  CAS  Google Scholar 

  • Chen EP, Bittner HB, Davis RD, Van Trigt P, Folz RJ (1998) Physiological effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury. J Thorac Cardiovasc Surg 115:450–458

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Mohuczy D, Li D, Kimura B, Phillips MI, Mehta P, Mehta JL (2001) Protection against ischemia/reperfusion injury and myocardial dysfunction by antisenseoligodeoxynucleotide directed at angiotensin-converting enzyme mRNA. Gene Ther 8:804–810

    Article  PubMed  CAS  Google Scholar 

  • Chirmule N, Propert K, Magosin S, Qian Y, Qian R, Wilson J (1999) Immune responses to adenovirus and adeno associated virus in humans. Gene Ther 6:1574–1583

    Article  PubMed  CAS  Google Scholar 

  • Colucci WS (1997) Molecular and cellular mechanisms of myocardial failure. Am J Cardiol 80:15L–25L

    Article  PubMed  CAS  Google Scholar 

  • D’Agostino RB, Russel MW, Huse DM, Ellison RC, Silbershantz H, Wilson PW, Hartz SC (2000) Primary and subsequent coronary risk appraisal: new results from the Framingham study. Am Heart J 139:272–281

    Article  PubMed  CAS  Google Scholar 

  • Edelstein ML, Abedi MR, Wixon J, Edelstein RM (2004) Gene therapy clinical trials worldwide 1989–2002—an overview. J Gene Med 6:597–602

    Article  PubMed  Google Scholar 

  • Feldman LJ, Steg G (1997) Optimal techniques for arterial gene transfer. Cardiovasc Res 35:391–404

    Article  PubMed  CAS  Google Scholar 

  • Funk M, Krumholz HM (1996) Epidemiologic and economic impact of advanced heart failure. J Cardiovasc Nurs 10:1–10

    PubMed  CAS  Google Scholar 

  • Giordano FJ, Ping P, McKirnan MD, Nozaki S, DeMaria AN, Dillmann WH, Mathieu-Costello O, Hammond HK (1996) Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat Med 2:534–539

    Article  PubMed  CAS  Google Scholar 

  • Givertz MM, Colucci WS (1998) New targets for heart failure therapy: endothelin, inflammatory cytokines, and oxidative stress. Lancet 352:S134–S138

    Article  Google Scholar 

  • Grines CL, Watkins MW, Helmer G, Penny W, Brinker J, Marmur JD, West A, Rade JJ, Marrott P, Hammond HK, Engler RL (2002) Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation 105:1291–1297

    Article  PubMed  CAS  Google Scholar 

  • Isner JM (2002) Myocardial gene therapy. Nature 415:234–239

    Article  PubMed  CAS  Google Scholar 

  • Kannel WB, Belanger AJ (1991) Epidemiology of heart failure. Am Heart J 12:951–957

    Article  Google Scholar 

  • Kaplitt MG, Xiao X, Samulski RJ, Li J, Ojamaa K, Klein IL, Makimura H, Kaplitt MJ, Strumpf RK, Diethrich EB (2000) Long term gene transfer in porcine myocardium after coronary infusion of and adeno-associated virus vector. Ann Thorac Surg 62:1669–1676

    Article  Google Scholar 

  • Klagsbrun M (1989) The fibroblast growth factor family: structural and biological properties. Prog Growth Factor Res 1:207–235

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, Kajstura J, Baerga R, Anversa P (1997) Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest 100:1991–1999

    PubMed  CAS  Google Scholar 

  • Li Q, Bolli R, Qiu Y, Tang XL, Guo Y, French BA (2001) Gene therapy with extracellular super-oxide dismutase protects conscious rabbits against myocardial infarction. Circulation 103:1893–1898

    PubMed  CAS  Google Scholar 

  • Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, Ashare AB, Lathi K, Isner JM (1998) Gene therapy for myocardial angiogenesis. Initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98:2800–2804

    PubMed  CAS  Google Scholar 

  • Mack CA, Patel SA, Schwarz EA, Zanzonico P, Hahn RT, Hercil A, Devereux RB, Goldsmith SJ, Christian TF, Sanborn TA, Kovesdi I, Hackett N, Isom OW, Crystal RG, Rosengart J (1998) Biological bypass with the use of adenovirus-mediated transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg 115:168–177

    Article  PubMed  CAS  Google Scholar 

  • Mah C, Byrne BJ, Flotte TR (2002) Virus-based gene delivery systems. Clin Pharmacokinet 41:901–911

    Article  PubMed  CAS  Google Scholar 

  • Mann MJ, Dzau VJ (2000) Therapeutic applications of transcription factor decoy oligonucleotides. J Clin Invest 106:1071–1075

    PubMed  CAS  Google Scholar 

  • Mann MJ, Whittemore AD, Donaldson MC, Belkin M, Conte MS, Polak JF, Orav EJ, Ehsan A, Dell’Acqua G, Dzau VJ (1999) Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomized, controlled trial. Lancet 354:1493–1498

    Article  PubMed  CAS  Google Scholar 

  • Masaki I, Yonemitsu Y, Yamashita A, Sata S, Tanii M, Komori K, Nakagawa K, Hou X, Nagai Y, Hasegawa M, Sugimachi K, Sueishi K (2002) Angiogenic gene therapy for experimental critical limb ischemia: acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2. Circ Res 90:966–973

    Article  PubMed  CAS  Google Scholar 

  • McCarthy M (2001) Molecular decoy may keep bypass grafts open. Lancet 358:1703

    Google Scholar 

  • McMurray JC, Pfeffer MA (2002) New therapeutic options in congestive heart failure. Circulation 105:2099–2106

    Article  PubMed  Google Scholar 

  • Mehta JL, Li DY (1999) Inflammation in ischemic heart disease: response to tissue injury or a pathogenic villain? Cardiovasc Res 43:291–299

    Article  PubMed  CAS  Google Scholar 

  • Melo LG, Agrawal R, Zhang L, Rezvani M, Mangi AA, Ehsan E, Griese DP, Dell’Acqua G, Mann MJ, Oyama J, Yet SF, Layne MD, Perrella AM, Dzau VJ (2002) Gene Therapy strategy for long term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 105:602–607

    Article  PubMed  CAS  Google Scholar 

  • Melo LG, Pachori AS, Kong D, et al (2004) Gene and cell-based therapies for heart disease. FASEB J 18:648–663

    Article  PubMed  CAS  Google Scholar 

  • Monahan PE, Samulski RJ (2000) Adeno-associated virus vectors for gene therapy: more pros than cons? Mol Med Today 6:433–440

    Article  PubMed  CAS  Google Scholar 

  • Morishita R, Sugimoto T, Aoki M, Kida I, Tomita N, Moriguchi A, Maeda K, Sawa Y, Kaneda Y, Higaki J, Ogihara T (1997) In vivo transfection of cis element “decoy” against nuclear factor factor κB binding sites prevents myocardial infarction. Nat Med 3:894–899

    Article  PubMed  CAS  Google Scholar 

  • Niidome T, Huang L (2002) Gene therapy progress and prospects: non-viral vectors. Gene Ther 9:1647–1652

    Article  PubMed  CAS  Google Scholar 

  • Pachori AS, Numan MT, Ferrario CM, Diz DM, Raizada MK, Katovich MJ (2002) Blood pressure-independent attenuation of cardiac hypertrophy by AT(1)R-AS gene therapy. Hypertension 20:969–975

    Article  CAS  Google Scholar 

  • Park JL, Lucchesi BR (1999) Mechanisms of myocardial reperfusion injury. Ann Thorac Surg 68:1905–1912

    Article  PubMed  CAS  Google Scholar 

  • Peterson JT, Li H, Dillon L, Bryant JW (2000) Evolution of metalloprotease and tissue inhibitor expression during heart failure progression in the infarcted heart. Cardiovasc Res 46:307–315

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer JM, Pfeffer MA, Fletcher PJ, Braunwald E (1991) Progressive ventricular remodelling in rat myocardial infarction. Am J Physiol 260:H1406–H1414

    PubMed  CAS  Google Scholar 

  • Poston RS, Mann MJ, Hoyt EG, Ennen M, Dzau VJ, Robbins RC (1999) Antisense oligodeoxynucleotides prevent acute cardiac allograft rejection via a novel, non-toxic, highly efficient transfection method. Transplantation 68:825–832

    Article  PubMed  CAS  Google Scholar 

  • Robbins PD, Ghivizzani SC (1998) Viral vectors for gene therapy. Pharmacol Ther 80:35–47:1998

    Article  PubMed  CAS  Google Scholar 

  • Sharif F, Daly K, Crowley J, O’Brien T (2004) Current status of catheter-and stent-based gene therapy. Cardiovasc Res 64:208–216

    Article  PubMed  CAS  Google Scholar 

  • Stein CA (2001) The experimental use of antisense oligonucleotides: a guide for the perplexed. J Clin Invest 108:641–644

    Article  PubMed  CAS  Google Scholar 

  • Stein EA (2002) Identification and treatment of individuals at high risk of coronary artery disease. Am J Med 112Suppl 8A:3S–9S

    Article  PubMed  Google Scholar 

  • Stepkowski SM (2000) Development of antisense oligodeoxynucleotides for transplantation. Curr Opin Mol Ther 2:304–317

    PubMed  CAS  Google Scholar 

  • Sutton MG, Sharpe N (2000) Left ventricular remodeling aftermyocardial infarction. Pathophysiology and therapy. Circulation 101:2981–2988

    PubMed  CAS  Google Scholar 

  • Sylven C, Sarkar N, Insulander P, Kenneback G, Blomberg P, Islam K, Drvota V (2002) Catheter-based transendocardial myocardial gene transfer. J Interv Cardiol 15:7–13

    PubMed  Google Scholar 

  • Symes JF, Losordo DW, Vale PR, Lathi KG, Esakof DD, Mayskiy M, Isner JM (1999) Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thorac Surg 68:830–837

    Article  PubMed  CAS  Google Scholar 

  • Taigen T, Windt LJ, Lim HW, Molkentin JD (2000) Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy. Proc Natl Acad Sci USA 97:1196–1201

    Article  PubMed  CAS  Google Scholar 

  • Tio RA, Tkebuchava T, Scheurermann TH, Lebherz C, Magner M, Kearny M, Esakof DD, Isner JM, Symes JF (1999) Intramyocardial gene therapy with naked DNA encoding vascular endothelial growth factor improves collateral blood flow to ischemic myocardium. Hum Gene Ther 10:2953–2960

    Article  PubMed  CAS  Google Scholar 

  • Ueda H, Sawa Y, Matsumoto K, Kitagawa-Sakakida S, Kawahira Y, Nakamura T, Kaneda Y, Matsuda H (1999) Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart. Ann Thorac Surg 67:1726–1731

    Article  PubMed  CAS  Google Scholar 

  • Ueno H, Li JJ, Masuda S, Qi Z, Yamamoto H, Takeshita A (1997) Adenovirus-mediated expression of the secreted form of basic fibroblast growth factor (FGF-2) induces cellular proliferation and angiogenesis in vivo. Arterioscler Thromb Vasc Biol 17:2453–2460

    PubMed  CAS  Google Scholar 

  • Vajanto I, Rissanen TT, Rutanen J, Hiltunen MO, Tuomisto TT, Arve K, Narvanen O, Manninen H, Rasanen H, Hippelainen M, Alhava E, Yla-Herttuala S (2002) Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. J Gene Med 4:371–380

    Article  PubMed  CAS  Google Scholar 

  • Vale PR, Losordo DW, Milliken CE, McDonald MC, Gravelin LM, Curry CM, Esakof DD, Maysky M, Symes JF, Isner JM (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 

  • Ware JH, Simons M (1997) Angiogenesis in ischemic heart disease. Nat Med 3:158–164

    Article  PubMed  CAS  Google Scholar 

  • White RR, Sullenger BA, Rusconi CP (2000) Developing aptamers into therapeutics. J Clin Invest 106:929–934

    PubMed  CAS  Google Scholar 

  • Williams RS, Benjamin IJ (2000) Protective responses of the ischemic myocardium. J Clin Invest 106:813–818

    Article  PubMed  CAS  Google Scholar 

  • Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847

    PubMed  CAS  Google Scholar 

  • Yellon DM, Baxter GF (2000) Reperfusion injury revisited. Is there a role for growth factor signalling in limiting lethal reperfusion injury? Trends Cardiovasc Med 9:245–249

    Article  Google Scholar 

  • Yla-Herttuala S, Alitalo K (2003) Gene transfer as a tool to induce therapeutic vascular growth. Nat Med 9:694–700

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Pachori, A.S., Melo, L.G., Dzau, V.J. (2006). Gene Therapy: Role in Myocardial Protection. In: Moncada, S., Higgs, A. (eds) The Vascular Endothelium II. Handbook of Experimental Pharmacology, vol 176/II. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-36028-X_11

Download citation

Publish with us

Policies and ethics