Gene Therapy pp 131-151 | Cite as

Cardiovascular Gene Therapy

  • R. Engler
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 27)

Abstract

We are poised on the threshold of a new era; the ability to alter the genetic make up and/or expression of genes in humans. The prospect is a single injection of a gene therapeutic curing familial hypercholesterolemia, correcting severe combined immunodeficiency, removing the death sentence from those with a hereditary colon cancer gene, or growing new blood vessels to relieve chronic myocardial ischemia. The last decade has seen much progress toward reaching these goals, but we are not there yet. We review here the status of cardiovascular gene therapy in the published literature as of February 1998; mindful of the rapidly moving field we are surveying.

Keywords

Placebo Cholesterol Toxicity Ischemia Lipase 

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References

  1. Aoki M, Morishita R, Muraishi A, Moriguchi A, Sugimoto T, Maeda K, Dzau VJ, Kaneda Y, Higaki J, Ogihara T (1997) Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (hemag-glutinating virus of Japan)-liposome method. J Mol Cell Cardiol 29:949–959PubMedCrossRefGoogle Scholar
  2. 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:II 365–371CrossRefGoogle Scholar
  3. Asahara T, Chen D, Tsurumi Y, Kearney M, Rossow S, Passeri J, Symes JF, Isner JM (1996) Accelerated restitution of endothelial integrity and endothe-lium-dependent function after phVEGF165 gene transfer. Circulation 94:3291–3302PubMedCrossRefGoogle Scholar
  4. Barr E, Carroll J, Kalynych AM, Tripathy SK, Kozarsky K, Wilson JM, Leiden JM (1994) Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Ther 1:51–58PubMedGoogle Scholar
  5. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC (1995) A role for CD95 ligand in preventing graft rejection (see comments). Nature 377:630–632PubMedCrossRefGoogle Scholar
  6. Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW (1997) Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275:1320–1323PubMedCrossRefGoogle Scholar
  7. Chao J, Chao L (1997) Experimental kallikrein gene therapy in hypertension, cardiovascular and renal diseases. Pharmacol Res 35:517–522PubMedCrossRefGoogle Scholar
  8. 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 (see comments). Nat Med 2:534–539PubMedCrossRefGoogle Scholar
  9. Gottlieb RA, Burleson KO, Kloner RA, Babior BM, Engler RL (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621–1628PubMedCrossRefGoogle Scholar
  10. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA (1995) Fas li-gand-induced apoptosis as a mechanism of immune privilege. Science 270:1189–1192PubMedCrossRefGoogle Scholar
  11. Guzman RJ, Hirschowitz EA, Brody SL, Crystal RG, Epstein SE, Finkel T (1994) In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci USA 91:10732–10736PubMedCrossRefGoogle Scholar
  12. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF (1996) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 348:370–374PubMedCrossRefGoogle Scholar
  13. Kaplitt MG, Xiao X, Samulski RJ, Li J, Ojamaa K, Klein IL, Makimura H, Kaplitt MJ, Strumpf RK, Diethrich EB (1996) Long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector. Ann Thorac Surg 62:1669–1676PubMedCrossRefGoogle Scholar
  14. Kim S, Lin H, Barr E, Chu L, Leiden JM, Parmacek MS (1997) Transcriptional targeting of replication-defective adenovirus transgene expression to smooth muscle cells in vivo. J Clin Invest 100:1006–1014PubMedCrossRefGoogle Scholar
  15. Lau HT, Yu M, Fontana A, Stoeckert CJ (1996) Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 273:109–112PubMedCrossRefGoogle Scholar
  16. Lazarous DF, Shou M, Scheinowitz M, Hodge E, Thirumurti V, Kitsiou AN, Stiber JA, Lobo AD, Hunsberger S, Guetta E, Epstein SE, Unger EF (1996) Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury. Circulation 94:1074–1082PubMedCrossRefGoogle Scholar
  17. Li J, Fang B, Eisensmith RC, Li XH, Nasonkin I, Lin-Lee YC, Mims MP, Hughes A, Montgomery CD, Roberts JD (1995) In vivo gene therapy for hyperlipidemia: phenotypic correction in Watanabe rabbits by hepatic delivery of the rabbit LDL receptor gene. J Clin Invest 95:768–773PubMedCrossRefGoogle Scholar
  18. Libby P (1998) Gene therapy of restenosis. Circ Res 82:404–406 (abstract)PubMedCrossRefGoogle Scholar
  19. Lin KF, Chao L, Chao J (1997) Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension 30:307–313PubMedCrossRefGoogle Scholar
  20. Mack CA, Patel SR, Schwarz EA, Zanzonico P, Hahn RT, Ilercil A, Devereux RB, Goldsmith SJ, Christian TF, Sanborn TA, Kovesdi I, Hackett N, Isom OW, Crystal RG, Rosengart TK (1998) Biologic bypass with the use of ade-novirus-mediated gene 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 115:168–176; discussion 176–177PubMedCrossRefGoogle Scholar
  21. Mathias P, Wickham T, Moore M, Nemerow G (1994) Multiple adenovirus serotypes use alpha v integrins for infection. J Virol 68:6811–6814PubMedGoogle Scholar
  22. Murry CE, Kay MA, Bartosek T, Hauschka SD, Schwartz SM (1996) Muscle differentiation during repair of myocardial necrosis in rats via gene transfer with MyoD. J Clin Invest 98:2209–2217PubMedCrossRefGoogle Scholar
  23. Roth DM, Maruoka Y, Rogers J, White FC, Longhurst JC, Bloor CM (1987) Development of coronary collateral circulation in left circumflex ameroid-occluded swine myocardium. Am J Physiol 253:H1279-H1288PubMedGoogle Scholar
  24. Roth DM, White FC, Nichols ML, Dobbs SL, Longhurst JC, Bloor CM (1990) Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs. Circulation 82:1778–1789PubMedCrossRefGoogle Scholar
  25. Schulick AH, Vassalli G, Dunn PF, Dong G, Rade JJ, Zamarron C, Dichek DA (1997) Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity. J Clin Invest 99:209–219PubMedCrossRefGoogle Scholar
  26. Schumacher B, Pecher P, von Specht BU, Stegmann T (1998) Induction of neoangiogenesis in ischemic myocardium by human growth factors. Circulation 97:645–650PubMedCrossRefGoogle Scholar
  27. Smith TA, White BD, Gardner JM, Kaleko M, McClelland A (1996) Transient immunosuppression permits successful repetitive intravenous administration of an adenovirus vector. Gene Ther 3:496–502PubMedGoogle Scholar
  28. Sosnowski BA, Gonzalez AM, Chandler LA, Buechler YJ, Pierce GF, Baird A (1996) Targeting DNA to cells with basic fibroblast growth factor (FGF2). J Biol Chem 271:33647–33653PubMedCrossRefGoogle Scholar
  29. Takeshita S, Tsurumi Y, Couffinahl T, Asahara T, Bauters C, Symes J, Ferrara N, andIsner JM (1996) Gene transfer of naked DNA encoding for three iso-forms of vascular endothelial growth factor stimulates collateral development in vivo. Lab Invest 75:487–501PubMedGoogle Scholar
  30. Takeshita S, Weir L, Chen D, Zheng LP, Riessen R, Bauters C, Symes JF, Ferrara N, Isner JM (1996) Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 227:628–635PubMedCrossRefGoogle Scholar
  31. Tsunami Y, Takeshita S, Chen D, Kearney M, Rossow ST, Passeri J, Horowitz JR, Symes JF, Isner JM (1996) Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion (see comments). Circulation 94:3281–3290CrossRefGoogle Scholar
  32. Van Belle E, Tio FO, Chen D, Maillard L, Kearney M, Isner JM (1997) Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimai thickening. J Am Coll Cardiol 29:1371–1379PubMedCrossRefGoogle Scholar
  33. Wickham TJ, Filardo EJ, Cheresh DA, Nemerow GR (1994) Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabili-zation. J Cell Biol 127:257–264PubMedCrossRefGoogle Scholar
  34. Wickham TJ, Mathias P, Cheresh DA, Nemerow GR (1993) Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 73:309–319PubMedCrossRefGoogle Scholar
  35. Yang HT, Deschenes MR, Ogilvie RW, Terjung RL (1996) Basic fibroblast growth factor increases collateral blood flow in rats with femoral arterial ligation. Circ Res 79:62–69PubMedCrossRefGoogle Scholar
  36. Yang Y, Ertl HC, Wilson JM (1994) MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with El-deleted recombinant adenoviruses. Immunity 1:433–442PubMedCrossRefGoogle Scholar
  37. Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM (1994) Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91:4407–4411PubMedCrossRefGoogle Scholar
  38. Yang Y, Nunes FA, Berencsi K, Gonczol E, Engelhardt JF, Wilson JM (1994) Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nat Genet 7:362–369PubMedCrossRefGoogle Scholar
  39. Yang, Y, Trinchieri G, Wilson JM (1995) Recombinant IL-12 prevents formation of blocking IgA antibodies to recombinant adenovirus and allows repeated gene therapy to mouse lung (see comments). Nat Med 1:890–893PubMedCrossRefGoogle Scholar
  40. Yang Y, Wilson JM (1995) Clearance of adenovirus-infected hepatocytes by MHC class I-restricted CD4+ CTLs in vivo. J Immunol 155:2564–2570PubMedGoogle Scholar
  41. Zoldhelyi P, McNatt J, Xu XM, Loose-Mitchell D, Meidell RS, Clubb FJ, Buja LM, Willerson JT, Wu KK (1996) Prevention of arterial thrombosis by ade-novirus-mediated transfer of cyclooxygenase gene. Circulation 93:10–17PubMedCrossRefGoogle Scholar
  42. Zwiebel JA, Freeman SM, Kantoff PW, Cornetta K, Ryan US, Anderson WF (1989) High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors. Science 243:220–222PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

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  • R. Engler

There are no affiliations available

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