Skip to main content
SpringerLink
Log in

Gene Therapy for Angiogenesis in the Treatment of Cardiovascular and Peripheral Arterial Disease

  • Chapter
Angiogenesis and Direct Myocardial Revascularization

Part of the book series: Contemporary Cardiology ((CONCARD))

  • 371 Accesses

Abstract

Over the last quarter-century, numerous advances have been made in the understanding of the molecular and cellular processes that lead to the development of atherosclerosis. The respective roles of the endothelium, inflammatory mediators, and thrombosis in the pathogenesis of vascular disease are beginning to be better understood. As more is learned about the initiation of atherosclerotic cardiovascular disease, new targets for systemic therapies are being discovered. Several classes of medications have been shown to be beneficial in preventing adverse cardiovascular events in patients with cardiovascular disease. These medications include platelet inhibitors (aspirin and thienopyridines), angiotensin-converting enzyme inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (“statins”).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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.

Similar content being viewed by others

References

  1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–1186.

    PubMed  CAS  Google Scholar 

  2. Risau W. Differentiation of endothelium. FASEB J 1995;9:926–933.

    PubMed  CAS  Google Scholar 

  3. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931–10934.

    PubMed  CAS  Google Scholar 

  4. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671–674.

    PubMed  CAS  Google Scholar 

  5. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–967.

    PubMed  CAS  Google Scholar 

  6. Takahashi T, Kalka C, Masuda H, et al. Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999;5:434–438.

    PubMed  CAS  Google Scholar 

  7. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.

    PubMed  CAS  Google Scholar 

  8. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000;97:3422–3427.

    PubMed  CAS  Google Scholar 

  9. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002;360:427–435.

    PubMed  Google Scholar 

  10. Arras M, Ito WD, Scholz D, Winkler B, Schaper J, Schaper W. Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. J Clin Invest 1998;101:40–50.

    PubMed  CAS  Google Scholar 

  11. Takeshita S, Weir L, Chen D, et al. Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 1996;227:628–635.

    PubMed  CAS  Google Scholar 

  12. Brogi E, Schatteman G, Wu T, et al. Hypoxia-induced paracrine regulation of VEGF receptor expression. J Clin Invest 1996;97:469–476.

    PubMed  CAS  Google Scholar 

  13. Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376:66–70.

    PubMed  CAS  Google Scholar 

  14. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1 deficient mice. Nature 1995;376:62–66.

    PubMed  CAS  Google Scholar 

  15. Carmeliet P, Collen D. Molecular analysis of blood vessel formation and disease. Am J Physiol 1997;273:H2091–H2104.

    PubMed  CAS  Google Scholar 

  16. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 1997;276:1423–1425.

    PubMed  CAS  Google Scholar 

  17. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246:1306–1309.

    PubMed  CAS  Google Scholar 

  18. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161:851–855.

    PubMed  CAS  Google Scholar 

  19. Conn G, Soderman D, Schaeffer M-T, Wile M, Hatcher VB, Thomas KA. Purification of glycoprotein vascular endothelial cell mitogen from a rat glioma cell line. Proc Natl Acad Sci USA 1990;87:1323–1327.

    PubMed  CAS  Google Scholar 

  20. Kalka C, Masuda H, Takahashi T, et al. Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res 2000;86:1198–1202.

    PubMed  CAS  Google Scholar 

  21. Asahara T, Takahashi T, Masuda H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 1999;18:3964–3972.

    PubMed  CAS  Google Scholar 

  22. Kalka C, Tehrani H, Laudenberg B, et al. Mobilization of endothelial progenitor cells following gene therapy with VEGF165 in patients with inoperable coronary disease. Ann Thorac Surg 2000;70:829–834.

    PubMed  CAS  Google Scholar 

  23. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000;6:389–395.

    PubMed  CAS  Google Scholar 

  24. Tabata H, Silver M, Isner JM. Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA. Cardiovasc Res 1997;35:470–479.

    PubMed  CAS  Google Scholar 

  25. Giordano FJ, Ping P, McKirnan MD, et al. Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat Med 1996;2:534–539.

    PubMed  CAS  Google Scholar 

  26. McKirnan MD, Guo X, Waldman LK, et al. Intracoronary gene transfer of fibroblast growth factor-4 increases regional contractile function and responsiveness to adrenergic stimulation in heart failure. Cardiac Vasc Regen 2000;1:11–21.

    Google Scholar 

  27. Takeshita S, Isshiki T, Sato T. Increased expression of direct gene transfer into skeletal muscles observed after acute ischemic injury in rats. Lab Invest 1996;74:1061–1065.

    PubMed  CAS  Google Scholar 

  28. Tsurumi Y, Takeshita S, Chen D, et al. Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation 1996;94:3281–3290.

    PubMed  CAS  Google Scholar 

  29. Takeshita S, Losordo DW, Kearney M, Isner JM. Time course of recombinant protein secretion following liposome-mediated gene transfer in a rabbit arterial organ culture model. Lab Invest 1994;71:387–391.

    PubMed  CAS  Google Scholar 

  30. Losordo DW, Pickering JG, Takeshita S, et al. Use of the rabbit ear artery to serially assess foreign protein secretion after site specific arterial gene transfer in vivo: Evidence that anatomic identification of successful gene transfer may underestimate the potential magnitude of transgene expression. Circulation 1994;89:785–792.

    PubMed  CAS  Google Scholar 

  31. Ischemia EWGoCL. Second European consensus document on chronic critical leg ischemia. Circulation 1991;84:IV-1–IV-26.

    Google Scholar 

  32. Treat-Jacobson D, Halverson SL, Ratchford A, Regensteiner JG, Lindquist R, Hirsch AT. A patient-derived perspective of health related quality of life with peripheral arterial disease. J Nurs Scholarship 2002;34:55–60.

    Google Scholar 

  33. Eneroth M, Persson BM. Amputation for occlusive arterial disease. A multicenter study of 177 amputees. Int Orthop 1992;16:382–387.

    Google Scholar 

  34. Campbell WB, Johnston JA, Kernick VF, Rutter EA. Lower limb amputation: striking the balance. Ann Royal Coll Surg Engl 1994;76:205–209.

    CAS  Google Scholar 

  35. Dawson I, Keller BP, Brand R, Pesch-Batenburg J, Hajo van Bockel J. Late outcomes of limb loss after failed infrainguinal bypass. J Vasc Surg 1995;21:613–622.

    PubMed  CAS  Google Scholar 

  36. Skinner JA, Cohen AT. Amputation for premature peripheral atherosclerosis: do young patients do better? Lancet 1996;348:1396.

    PubMed  CAS  Google Scholar 

  37. Takeshita S, Zheng LP, Brogi E, et al. Therapeutic angiogenesis: a single intra-arterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hindlimb model. J Clin Invest 1994;93:662–670.

    PubMed  CAS  Google Scholar 

  38. Connolly DT, Hewelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clinl Invest 1989;84:1470–1478.

    CAS  Google Scholar 

  39. Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis following arterial gene transfer of phVEGF165. Lancet 1996;348:370–374.

    PubMed  CAS  Google Scholar 

  40. Feldman LJ, Steg PG, Zheng LP, et al. Low-efficiency of percutaneous adenovirus-mediated arterial gene transfer in the atherosclerotic rabbit. J Clin Invest 1995;95:2662–2671.

    PubMed  CAS  Google Scholar 

  41. Rivard A, Silver M, Chen D, et al. Rescue of diabetes related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol 1999;154:355–364.

    PubMed  CAS  Google Scholar 

  42. Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 following intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998;97:1114–1123.

    PubMed  CAS  Google Scholar 

  43. Rauh G, Gravereaux EC, Pieczek AM, Radley S, Schainfeld RM, Isner JM. Age <50 years and rest pain predict positive clinical outcome after intramuscular gene transfer of phVEGF165 in patients with critical limb ischemia. Circulation 1999;100:I–319.

    Google Scholar 

  44. Baumgartner I, Rauh G, Pieczek A, et al. Lower-extremity edema associated with gene transfer of naked DNA vascular endothelial growth factor. Ann Int Med 2000;132:880–884.

    PubMed  CAS  Google Scholar 

  45. Isner JM, Baumgartner I, Rauh G, et al. Treatment of thromboangiitis obliterans (Buerger’s disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg 1998;28:964–975.

    PubMed  CAS  Google Scholar 

  46. Witzenbichler B, Asahara T, Murohara T, et al. Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. Am J Pathol 1998;153:381–394.

    PubMed  CAS  Google Scholar 

  47. Rajagopalan S, Shah M, Luciano A, Crystal R, Nabel EG. Adenovirus-mediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve. Circulation 2001;104:753–755.

    PubMed  CAS  Google Scholar 

  48. Asahara T, Bauters C, Pastore CJ, et al. Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery. Circulation 1995;91:2793–2801.

    PubMed  CAS  Google Scholar 

  49. Asahara T, Chen D, Tsurumi Y, et al. Accelerated restitution of endothelial integrity and endothelium-dependent function following phVEGF165 gene transfer. Circulation 1996;94:3291–3302.

    PubMed  CAS  Google Scholar 

  50. Van Belle E, Tio FO, Couffinhal T, Maillard L, Passeri J, Isner JM. Stent endothelialization: time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition. Circulation 1997;95:438–448.

    PubMed  Google Scholar 

  51. Van Belle E, Tio FO, Chen D, Maillard L, Kearney M, Isner JM. Passivation of metallic stents following arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening. J Am Coll Cardiol 1997;29:1371–1379.

    PubMed  Google Scholar 

  52. Minar E, Pokrajac B, Maca T, et al. Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty: results of a prospective randomized study. Circulation 2000;102:2694–2699.

    PubMed  CAS  Google Scholar 

  53. Hendel RC, Henry TD, Rocha-Singh K, et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dose-dependent effect. Circulation 2000;101:118–121.

    PubMed  CAS  Google Scholar 

  54. Henry TD, Abraham JA. Review of prelcinical and clinical results with vascular endothelial growth factors for therapeutic angiogenesis. Curr Intervent Cardiol Rep 2000;2:228–241.

    Google Scholar 

  55. Henry TD, Rocha-Singh K, Isner JM, et al. Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease. Am Heart J 2001;142:872–880.

    PubMed  CAS  Google Scholar 

  56. Henry TD, Rocha-Singh K, Isner JM, et al. Results of intracoronary recombinant human vascular endothelial growth factor (rhVEGF) administration trial. J Am Coll Cardiol 1998;31:65A.

    Google Scholar 

  57. Henry TD, Annex BH, Azrin MA, et al. Final results of the VIVA trial of rhVEGF for human therapeutic angiogenesis. Circulation 1999;100:I–476.

    Google Scholar 

  58. Ferguson JJ. Meeting highlights: highlights of the 48th scientific sessions of the American College of Cardiology. Circulation 1999;100:570–575.

    PubMed  CAS  Google Scholar 

  59. Henry TD, McKendall GR, Azrin MA, et al. VIVA trial: one year follow up. Circulation 2000;102:II–309.

    Google Scholar 

  60. Hariawala MD, Horowitz JR, Esakof D, et al. VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts. J Surg Res 1996;63:77–82.

    PubMed  CAS  Google Scholar 

  61. Lopez JJ, Laham RJ, Stamler A, et al. VEGF administration in chronic myocardial ischemia in pigs. Cardiovasc Res 1998;40:272–281.

    PubMed  CAS  Google Scholar 

  62. Banai S, Jaklitsch MT, Shou M, et al. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 1994; 89:2183–2189.

    PubMed  CAS  Google Scholar 

  63. Hughes CG, Biswas SS, Yin B, et al. Intramyocardial but not intravenous vascular endothelial growth factor improves regional perfusion in hibernating porcine myocardium. Circulation 1999;100:I–476.

    Google Scholar 

  64. Harada K, Friedman M, Lopez JJ, et al. Vascular endothelial growth factor in chronic myocardial ischemia. Am J Physiol 1996;270:H1791–H1802.

    PubMed  CAS  Google Scholar 

  65. Mack CA, Patel SR, Schwarz EA, et al. Biologic bypass with the use of adenovirus-mediated gene transfer of the conplementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg 1998;115:168–176.

    PubMed  CAS  Google Scholar 

  66. Lee LY, Patel SR, Hackett NR, et al. Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endotehlial growth factor 121. Ann Thorac Surg 2000;69:14–24.

    PubMed  CAS  Google Scholar 

  67. Lazarous DF, Shou M, Stiber JA, et al. Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis. Cardiovasc Res 1999;44:294–302.

    PubMed  CAS  Google Scholar 

  68. Losordo DW, Vale PR, Symes J, et al. Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 1998;98:2800–2804.

    PubMed  CAS  Google Scholar 

  69. Symes JF, Losordo DW, Vale PR, et al. Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease: preliminary clinical results. Ann Thorac Surg 1999;68:830–837.

    PubMed  CAS  Google Scholar 

  70. Esakof DD, Maysky M, Losordo DW, et al. Intraoperative multiplane transesophageal echocardiograpy for guiding direct myocardial gene transfer of vascular endothelial growth factor in patients with refractory angina pectoris. Human Gene Ther 1999;10:2315–2323.

    Google Scholar 

  71. Shen Y-T, Vatner SF. Mechanism of impaired myocardial function during progressive coronary stenosis in conscious pigs: hibernation versus stunning? Circ Res 1995;76:479–488.

    PubMed  CAS  Google Scholar 

  72. Wijns W, Vatner SF, Camici PG. Hibernating myocardium. N Engl J Med 1998;3:173–181.

    Google Scholar 

  73. Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocardial viability in patients with hibernating and stunned myocardium. Circulation 1993;87:1–20.

    PubMed  CAS  Google Scholar 

  74. Vale PR, Losordo DW, Milliken CE, et al. Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia. Circulation 2000;102:965–974.

    PubMed  CAS  Google Scholar 

  75. Stewart JD. A phase 2 randomized, multicenter, 26-week study to assess the efficacy and safety of BIOBYPASS (adgfVEGF121.10) delivered through maximally invasive surgery versus maximal medical treatment in patients with severe angina, advanced coronary artery disease and no options for revascularization. Circulation 2002;106:2986–a.

    Google Scholar 

  76. Vale PR, Milliken CE, Tkebuchava T, et al. Catheter-based gene transfer of VEGF utilizing electromechanical LV mapping accomplishes therapeutic angiogenesis: pre-clinical studies in swine. Circulation 1999;100:I–512.

    Google Scholar 

  77. Vale PR, Losordo DW, Tkebuchava T, Chen D, Milliken CE, Isner JM. Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping. J Am Coll Cardiol 1999;34:246–254.

    PubMed  CAS  Google Scholar 

  78. Deutsch E, Tarazona N, Sanborn TA, et al. Percutaneous endocardial gene therapy: patterns of in-vivo gene expression related to regional myocardial delivery. J Am Coll Cardiol 2000;35:6A.

    Google Scholar 

  79. Kornowski R, Fuchs S, Vodovotz Y, et al. Catheter-based transendocardial injection of adenoviral VEGF121 offers equivalent gene delivery and protein expression compared to a surgical-based transepicardial injection approach. J Am Coll Cardiol 2000;35:73A.

    Google Scholar 

  80. Kornowski R, Leon MB, Fuchs S, et al. Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. J Am Coll Cardiol 2000;35:1031–1039.

    PubMed  CAS  Google Scholar 

  81. Vale PR, Losordo DW, Milliken CE, et al. Randomized, placebo-controlled clinical study of percutaneous catheter-based left ventricular endocardial gene transfer of VEGF-2 for myocardial ischemia. Circulation 2002;102:II–563.

    Google Scholar 

  82. Losordo DW, Vale PR, Hendel RC, et al. 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 2002;105:2012–2018.

    PubMed  CAS  Google Scholar 

  83. Walter DH, Cejna M, Diaz-Sandoval LJ, et al. Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis. Circulation 2002;106:II–125.

    Google Scholar 

  84. Hedman M, Hartikainen J, Syvanne M, et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia. Circulation 2003;107:2677–2683.

    PubMed  CAS  Google Scholar 

  85. Baffour R, Berman J, Garb JL, Rhee SW, Kaufman J, Friedmann P. Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant basic fibroblast growth factor in a rabbit model of acute lower limb ischemia: dose-response effect of basic fibroblast growth factor. J Vasc Surg 1992;16:181–191.

    PubMed  CAS  Google Scholar 

  86. Yang HT, Deschenes MR, Ogilvie RW, Terjung RL. Basic fibroblast growth factor increases collateral blood flow in rats with femoral arterial ligation. Circ Res 1996;79:62–69.

    PubMed  CAS  Google Scholar 

  87. Chlegoun JO, Martins RN, Mitchell CA, Chirila TV. Basic FGF enhances the development of collateral circulation after acute arterial occlusion. Biochem Biophys Res Commun 1992;185:510–516.

    Google Scholar 

  88. Lazarous DF, Unger EF, Epstein SE, et al. Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial. J Am Coll Cardiol 2000;36:1339–1344.

    Google Scholar 

  89. Lederman R. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC). Presented at Late-Breaking Clinical Trials session of 50th annual American College of Cardiology, Orlando, FL, March 19, 2001.

    Google Scholar 

  90. Comerota A, Throm R, Miller K, et al. Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial. J Vasc Surg 2002;35:930–936.

    PubMed  Google Scholar 

  91. Unger EF, Banai S, Shou M, et al. Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am J Physiol 1994;266:H1588–H1595.

    PubMed  CAS  Google Scholar 

  92. Lazarous DF, Scheinowtiz M, Shou M, et al. Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation 1995;91:145–153.

    PubMed  CAS  Google Scholar 

  93. Lazarous DF, Shou M, Scheinowitz M, et al. Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and arterial response to injury. Circulation 1996;94:1074–1082.

    PubMed  CAS  Google Scholar 

  94. Rajanayagam MA, Shou M, Thirumurti V, et al. Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusion in dogs. J Am Coll Cardiol 2000; 35:519–526.

    PubMed  CAS  Google Scholar 

  95. Schumacher B, Pecher P, von Specht BU, Stegmann T. Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. Circulation 1998;97:645–650.

    PubMed  CAS  Google Scholar 

  96. Schumacher B, Stegmann T, Pecher P. The stimulation of neoangiogenesis in the ischemic human heart by the growth factor FGF: first clinical results. J Cardiovas Surg 1998;39:783–789.

    CAS  Google Scholar 

  97. Stegmann TJ, Hoppert T, Schlurmann W, Gemeinhardt S. First angiogenic treatment of coronary heart disease by FGF-1: long-term results after 3 years. Cardiac Vasc Regen 2000;1:5–10.

    Google Scholar 

  98. Sellke FW, Laham RJ, Edelman ER, Pearlman JD, Simons M. Therapeutic angiogenesis with basic fibroblast growth factor: technique and early results. Ann Thorac Surg 1998;65:1540–1544.

    PubMed  CAS  Google Scholar 

  99. Laham RJ, Sellke FW, Edelman ER, et al. Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery: results of a phase 1 randomized, double-blind, placebo-controlled trial. Circulation 1999;100:1865–1871.

    PubMed  CAS  Google Scholar 

  100. Stegmann TJ, Hoppert T, Schneider A, et al. Induction of myocardial neoangiogenesis by human growth factors. A new therapeutic option in coronary heart disease. Herz 2000;25:589–599.

    PubMed  CAS  Google Scholar 

  101. Udelson JE, Dilsizian V, Laham RJ, et al. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease. Circulation 2000;102:1605–1610.

    PubMed  CAS  Google Scholar 

  102. Laham RJ, Chronos NA, Pike M, et al. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase 1 open-label dose escalation study. J Am Coll Cardiol 2000;36:2132–2139.

    PubMed  CAS  Google Scholar 

  103. Unger E, Goncalves L, Epstein S, et al. Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. Am J Cardiol 2000;85:1414–1419.

    PubMed  CAS  Google Scholar 

  104. Kleiman NS, Califf RM. Results from late-breaking clinical trials sessions at ACCIS 2000 and ACC 2000. J Am Coll Cardiol 2000;36:310–311.

    PubMed  CAS  Google Scholar 

  105. Harada K, Grossman W, Friedman M, et al. Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts. J Clin Invest 1994;94:623–630.

    PubMed  CAS  Google Scholar 

  106. Grines CL, Watkins MW, Helmer G, et al. Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris. Circulation 2002;105:1291–1297.

    PubMed  CAS  Google Scholar 

  107. Isner JM, Vale PR, Symes JF, Losordo DW. Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res 2001;895(5):389–400.

    Google Scholar 

  108. Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM. VEGF gene delivery to muscle: potential role of vasculogenesis in adults. Mol Cell 1998;2:549–558.

    PubMed  CAS  Google Scholar 

  109. Schwartz ER, Speakman MT, Patterson M, et al. Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the ratt—ngiogenesis and angioma formation. J Am Coll Cardiol 2000;35:1323–1330.

    Google Scholar 

  110. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–1487.

    PubMed  CAS  Google Scholar 

  111. Thurston G, Suri C, Smith K, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 1999;286:2511–2514.

    PubMed  CAS  Google Scholar 

  112. Hariawala M, Horowitz JR, Esakof D, et al. VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts. J Surg Res 1996;63:77–82.

    PubMed  CAS  Google Scholar 

  113. Horowitz JR, Rivard A, van der Zee R, et al. Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Arterioscler Thromb Vasc Biol 1997;17:2793–2800.

    PubMed  CAS  Google Scholar 

  114. van der Zee R, Murohara T, Luo Z, et al. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 1997;95:1030–1037.

    PubMed  Google Scholar 

  115. Murohara T, Asahara T, Silver M, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 1998;101:2567–2578.

    PubMed  CAS  Google Scholar 

  116. Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J. Angiogenesis inhibitors endostatin and TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999;99:1726–1732.

    PubMed  CAS  Google Scholar 

  117. Inoue M, Itoh H, Ueda M, et al. Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation 1998;98:2108–2116.

    PubMed  CAS  Google Scholar 

  118. Celletti FL, Waugh JM, Amabile PG, Brendolan A, Hilfiker PR, Dake MD. Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat Med 2001;7:425–429.

    PubMed  CAS  Google Scholar 

  119. Vale PR, Wuensch DI, Rauh GF, Rosenfield K, Schainfeld RM, Isner JM. Arterial gene therapy for inhibiting restenosis in patients with claudication undergoing superficial femoral artery angioplasty. Circulation 1998;98:I–66.

    Google Scholar 

  120. Laitinen M, Hartikainen J, Hiltunen MO, et al. Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Human Gene Ther 2000;11:263–270.

    CAS  Google Scholar 

  121. Takeshita S, Tsurumi Y, Couffinhal T, et al. Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 1996;75:487–502.

    PubMed  CAS  Google Scholar 

  122. Witzenbichler B, Asahara T, Murohara T, et al. Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. Am J Pathol 1998;153:381–394.

    PubMed  CAS  Google Scholar 

  123. Lopez JJ, Edelman ER, Stamler A, et al. Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia. Am J Physiol 1998;274:H930–H936.

    PubMed  CAS  Google Scholar 

  124. Vale PR, Rauh G, Wuensch DI, Pieczek A, Schainfeld RM. Influence of vascular endothelial growth factor on diabetic retinopathy. Circulation 1998;17:I–353.

    Google Scholar 

  125. Schofield PM, Sharples LD, Caine N, et al. Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial. Lancet 1999;353:519–524.

    PubMed  CAS  Google Scholar 

  126. Burkhoff D, Schmidt S, Schulman SP, et al. Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. Lancet 1999;354:885–890.

    PubMed  CAS  Google Scholar 

  127. Allen KB, Dowling RD, Fudge TL, et al. Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina. N Engl J Med 1999;341:1029–1036.

    PubMed  CAS  Google Scholar 

  128. Frazier OH, March RJ, Horvath KA, Group FtTCDLRS. Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med 1999;341:1021–1028.

    PubMed  CAS  Google Scholar 

  129. Aaberge L, Nordstrand K, Dragsund M, et al. Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris: clinical results from the Norwegian randomized trial. J Am Coll Cardiol 2000;35:1170–1177.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, St. Elizabeth’s Medical Center, Boston, MA

    Pinak B. Shah MD, Kapildeo Lotun MD & Douglas W. Losordo MD

Authors
  1. Pinak B. Shah MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kapildeo Lotun MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Douglas W. Losordo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Beth Israel Deaconess Medical Center, Boston, MA

    Roger J. Laham MD

  2. Brigham and Women’s Hospital, Boston, MA

    Donald S. Baim MD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Shah, P.B., Lotun, K., Losordo, D.W. (2005). Gene Therapy for Angiogenesis in the Treatment of Cardiovascular and Peripheral Arterial Disease. In: Laham, R.J., Baim, D.S. (eds) Angiogenesis and Direct Myocardial Revascularization. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59259-934-9_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-934-9_8

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-153-0

  • Online ISBN: 978-1-59259-934-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation