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01.08.2002 | Leading Article

Gene Therapy for Restenosis

Current Status

verfasst von: Juha Rutanen, Johanna Markkanen, Dr Seppo Ylä-Herttuala

Erschienen in: Drugs | Ausgabe 11/2002

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Abstract

Atherosclerosis is a major cause of morbidity and mortality in Western world. Vascular occlusion caused by atherosclerosis usually requires invasive treatment, such as surgical bypass or angioplasty However, bypass graft failure and restenosis limit the usefulness of these procedures, with 20% of patients needing a new revascularisation procedure within 6 months of angioplasty. Numerous pharmacological agents have been investigated for the prevention of restenosis but none has shown undisputed efficacy in clinical medicine.

Gene transfer offers a novel approach to the treatment of restenosis because of easy accessibility of vessels and already existing gene delivery methods. It can be used to overexpress therapeutically important proteins locally without high systemic toxicity, and the therapeutic effect can be targeted to a particular pathophysiological event. Promising results have been obtained from many pre-clinical experiments using therapeutic genes or oligonucleotides to prevent restenosis. Early clinical trials have shown that plasmid- and adenovirus-mediated vascular gene transfers can be conducted safely and are well tolerated. Ex vivo gene therapy with E2F-decoy succeeded in reducing graft occlusion rate after surgical bypass in a randomised, double-blind clinical trial.

In the future, further development of gene delivery methods and vectors is needed to improve the efficacy and safety of gene therapy. Also, better knowledge of vascular biology at the molecular level is needed to find optimal strategies and gene combinations to treat restenosis. Provided that these difficulties can be solved, gene therapy offers an enormous potential for clinical medicine in the future.

Bauters C, Meurice T, Hamon M, et al. Mechanisms and prevention of restenosis: from experimental models to clinical practice. Cardiovasc Res 1996; 31(6): 835–46PubMed

Narins CR, Holmes DRJ, Topol EJ. A call for provisional stenting: the balloon is back! Circulation 1998; 97(13): 1298–305PubMedCrossRef

Ylä-Herttuala S, Martin JF. Cardiovascular gene therapy. Lancet 2000; 355: 213–22PubMedCrossRef

Kim S, Lin H, Barr E, et al. Transcriptional targeting of replication-defective adenovirus transgene expression to smooth muscle cells in vivo. J Clin Invest 1997; 100(5): 1006–14PubMedCrossRef

Keogh MC, Chen D, Schmitt JF, et al. Design of a muscle cell-specific expression vector utilising human vascular smooth muscle alpha-actin regulatory elements. Gene Ther 1999; 6(4): 616–28PubMedCrossRef

Nicklin SA, White SJ, Watkins SJ, et al. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display. Circulation 2000; 102(2): 231–7PubMedCrossRef

Hall FL, Liu L, Zhu NL, et al. Molecular engineering of matrix-targeted retroviral vectors incorporating a surveillance function inherent in von Willebrand factor. Hum Gene Ther 2000; 11(7): 983–93PubMedCrossRef

Ribault S, Neuville P, Mechine-Neuville A, et al. Chimeric smooth muscle-specific enhancer/promoters: valuable tools for adenovirus-mediated cardiovascular gene therapy. Circ Res 2001; 88(5): 468–75PubMedCrossRef

Kibbe MR, Billiar TR, Tzeng E. Gene therapy for restenosis. Circ Res 2000; 86(8): 829–33PubMedCrossRef

10.

Laitinen M, Mäkinen K, Manninen H, et al. Adenovirus-mediated gene transfer to lower limb artery of patients with chronic critical leg ischemia. Hum Gene Ther 1998; 9(10): 1481–6PubMedCrossRef

11.

Mäkinen K, Laitinen M, Manninen H, et al. Catheter-mediated VEGF gene transfer to human lower limb arteries after PTA [abstract]. Circulation 1999; 100: (18) 1–770CrossRef

12.

Kovesdi I, Brough DE, Bruder JT, et al. Adenoviral vectors for gene transfer. Curr Opin Biotechnol 1997; 8(5): 583–9PubMedCrossRef

13.

Hiltunen MO, Turunen MP, Turunen AM, et al. Biodistribution of adenoviral vector to nontarget tissues after local in vivo gene transfer to arterial wall using intravascular and periadventitial gene delivery methods. FASEB J 2000; 14(14): 2230–6PubMedCrossRef

14.

Rutanen J, Rissanen TT, Kivela A, et al. Clinical applications of vascular gene therapy. Curr Cardiol Rep 2001; 3(1): 29–36PubMedCrossRef

15.

Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997; 275(5304): 1320–3PubMedCrossRef

16.

Tomko RP, Xu R, Philipson L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Natl Acad Sci U S A 1997; 94(7): 3352–6PubMedCrossRef

17.

Chu Y, Heistad D, Cybulsky MI, et al. Vascular cell adhesion molecule-1 augments adenovirus-mediated gene transfer. Arterioscler Thromb Vasc Biol 2001; 21(2): 238–42PubMedCrossRef

18.

Laitinen M, Pakkanen T, Donetti E, et al. Gene transfer into the carotid artery using an adventitial collar: comparison of the effectiveness of the plasmid- liposome complexes, retroviruses, pseudotyped retroviruses, and adenoviruses. Hum Gene Ther 1997; 8(14): 1645–50PubMedCrossRef

19.

Airenne KJ, Hiltunen MO, Turunen MP, et al. Baculovirus-mediated periadventitial gene transfer to rabbit carotid artery. Gene Ther 2000; 7(17): 1499–504PubMedCrossRef

20.

Lynch CM, Hara PS, Leonard JC, et al. Adeno-associated virus vectors for vascular gene delivery. Circ Res 1997; 80(4): 497–505PubMed

21.

Svensson EC, Marshall DJ, Woodard K, et al. Efficient and stable transduction of cardiomyocytes after intramyocardial injection or intracoronary perfusion with recombinant adeno-associated virus vectors. Circulation 1999; 99(2): 201–5PubMedCrossRef

22.

Laitinen M, Zachary I, Breier G, et al. Vegf gene transfer reduces intimai thickening via increased production of nitric oxide in carotid arteries. Hum Gene Ther 1997; 8(15): 1737–44PubMedCrossRef

23.

Turunen MP, Hiltunen MO, Ruponen M, et al. Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer-plasmid complexes. Gene Ther 1999; 6(1): 6–11PubMedCrossRef

24.

Sirois MG, Simons M, Edelman ER. Antisense oligonucleotide inhibition of PDGFR-beta receptor subunit expression directs suppression of intimai thickening. Circulation 1997; 95(3): 669–76PubMedCrossRef

25.

Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97(12): 1114–23PubMedCrossRef

26.

Laitinen M, Hartikainen J, Hiltunen MO, et al. Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Hum Gene Ther 2000; 11(2): 263–70PubMedCrossRef

27.

Varenne O, Gerard RD, Sinnaeve P, et al. Percutaneous adenoviral gene transfer into porcine coronary arteries: is catheter-based gene delivery adapted to coronary circulation? Hum Gene Ther 1999; 10(7): 1105–15PubMedCrossRef

28.

Bailey SR. Local drug delivery: current applications. Prog Cardiovasc Dis 1997; 40(2): 183–204PubMedCrossRef

29.

Schwartz RS. Pathophysiology of restenosis: interaction of thrombosis, hyperplasia, and/or remodeling. Am J Cardiol 1998; 81(7A): 14E–7EPubMedCrossRef

30.

Jawien A, Bowen-Pope DF, Lindner V, et al. Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest 1992; 89(2): 507–11PubMedCrossRef

31.

Stroobant P, Waterfield MD. Purification and properties of porcine platelet-derived growth factor. EMBO J 1984; 3(12): 2963–7PubMed

32.

Heldin CH, Johnsson A, Wennergren S, et al. A human osteosarcoma cell line secretes a growth factor structurally related to ahomodimer of PDGF A-chains. Nature 1986; 319(6053): 511–4PubMedCrossRef

33.

Hart CE, Forstrom JW, Kelly JD, et al. Two classes of PDGF receptor recognize different isoforms of PDGF. Science 1988; 240(4858): 1529–31PubMedCrossRef

34.

Li X, Ponten A, Aase K, et al. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol 2000; 2(5): 302–9PubMedCrossRef

35.

Gilbertson DG, Duff ME, West JW, et al. Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor. J Biol Chem 2001; 276(29): 27406–14PubMedCrossRef

36.

Bergsten E, Uutela M, Li X, et al. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol 2001; 3(5): 512–6PubMedCrossRef

37.

LaRochelle WJ, Jeffers M, McDonald WF, et al. PDGF-D, a new protease-activated growth factor. Nat Cell Biol 2001; 3(5): 517–21PubMedCrossRef

38.

Barrett TB, Benditt ER sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. Proc Natl Acad Sci U S A 1987; 84(4): 1099–103PubMedCrossRef

39.

Barrett TB, Benditt EP. Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall. Proc Natl Acad Sci U S A 1988; 85(8): 2810–4PubMedCrossRef

40.

Fingerle J, Johnson R, Clowes AW, et al. Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci U S A 1989; 86(21): 8412–6PubMedCrossRef

41.

Hart CE, Kraiss LW, Vergel S, et al. PDGFbeta receptor blockade inhibits intimai hyperplasia in the baboon. Circulation 1999; 99(4): 564–9PubMedCrossRef

42.

Ferns GA, Raines EW, Sprugel KH, et al. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 1991; 253(5024): 1129–32PubMedCrossRef

43.

Deguchi J, Namba T, Hamada H, et al. Targeting endogenous platelet-derived growth factor B-chain by adenovirus-mediated gene transfer potently inhibits in vivo smooth muscle proliferation after arterial injury. Gene Ther 1999; 6(6): 956–65PubMedCrossRef

44.

Cheng L, Mantile G, Pauly R, et al. Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo. Circulation 1998; 98(20): 2195–201PubMedCrossRef

45.

Pollman MJ, Hall JL, Mann MJ, et al. Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nat Med 1998; 4(2): 222–7PubMedCrossRef

46.

Morishita R, Higaki J, Tomita N, et al. Application of transcription factor “decoy” strategy as means of gene therapy and study of gene expression in cardiovascular disease. Circ Res 1998; 82(10): 1023–8PubMedCrossRef

47.

Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999; 77(7): 527–43PubMedCrossRef

48.

Asahara T, Bauters C, Pastore C, et al. Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimai hyperplasia in balloon-injured rat carotid artery. Circulation 1995; 91(11): 2793–801PubMedCrossRef

49.

Hiltunen MO, Laitinen M, Turunen MP, et al. Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointima formation in balloon-denuded rabbit aorta. Circulation 2000; 102(18): 2262–8PubMedCrossRef

50.

Hayashi K, Nakamura S, Morishita R, et al. In vivo transfer of human hepatocyte growth factor gene accelerates re-endothelialization and inhibits neointimal formation after balloon injury in rat model. Gene Ther 2000; 7(19): 1664–71PubMedCrossRef

51.

von der Leyen HE, Gibbons GH, Morishita R, et al. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A 1995; 92(4): 1137–41PubMedCrossRef

52.

Kullo IJ, Mozes G, Schwartz RS, et al. Adventitial gene transfer of recombinant endothelial nitric oxide synthase to rabbit carotid arteries alters vascular reactivity. Circulation 1997; 96(7): 2254–61PubMedCrossRef

53.

Janssens S, Flaherty D, Nong Z, et al. Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 1998; 97(13): 1274–81PubMedCrossRef

54.

Best PJ, Hasdai D, Sangiorgi G, et al. Apoptosis: basic concepts and implications in coronary artery disease. Arterioscler Thromb Vasc Biol 1999; 19(1): 14–22PubMedCrossRef

55.

Simari RD, San H, Rekhter M, et al. Regulation of cellular proliferation and intimai formation following balloon injury in atherosclerotic rabbit arteries. J Clin Invest 1996; 98(1): 225–35PubMedCrossRef

56.

Steg PG, Tahlil O, Aubailly N, et al. Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy. Circulation 1997; 96(2): 408–11PubMedCrossRef

57.

Rade JJ, Schulick AH, Virmani R, et al. Local adenoviral-mediated expression of recombinant hirudin reduces neointima formation after arterial injury. Nat Med 1996; 2(3): 293–8PubMedCrossRef

58.

Waugh JM, Kattash M, Li J, et al. Gene therapy to promote thromboresistance: local overexpression of tissue plasminogen activator to prevent arterial thrombosis in an in vivo rabbit model. Proc Natl Acad Sci U S A 1999; 96(3): 1065–70PubMedCrossRef

59.

Kakuta T, Currier JW, Haudenschild CC, et al. Differences in compensatory vessel enlargement, not intimai formation, account for restenosis after angioplasty in the hypercholesterolemic rabbit model. Circulation 1994; 89(6): 2809–15PubMedCrossRef

60.

Mintz GS, Popma JJ, Pichard AD, et al. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation 1996; 94(1): 35–43PubMedCrossRef

61.

Sangiorgi G, Taylor AJ, Farb A, et al. Histopathology of postpercutaneous transluminal coronary angioplasty remodeling in human coronary arteries. Am Heart J 1999; 138 (4 Pt 1): 681–7PubMedCrossRef

62.

Kumar A, Hoover JL, Simmons CA, et al. Remodeling and neointimal formation in the carotid artery of normal and P-selectin-deficient mice. Circulation 1997; 96(12): 4333–42PubMedCrossRef

63.

Kumar A, Lindner V. Remodeling with neointima formation in the mouse carotid artery after cessation of blood flow. Arterioscler Thromb Vasc Biol 1997; 17(10): 2238–44PubMedCrossRef

64.

Emanueli C, Salis MB, Chao J, et al. Adenovirus-mediated human tissue kallikrein gene delivery inhibits neointima formation induced by interruption of blood flow in mice. Arterioscler Thromb Vasc Biol 2001; 20(6): 1459–66CrossRef

65.

Komatsu R, Ueda M, Naruko T, et al. Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses. Circulation 1998; 98(3): 224–33PubMedCrossRef

66.

Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999; 99(1): 44–52PubMedCrossRef

67.

Brasen JH, Kivela A, Roser K, et al. Angiogenesis, vascular endothelial growth factor and platelet-derived growth factor-BB expression, iron deposition, and oxidation-specific epitopes in stented human coronary arteries. Arterioscler Thromb Vasc Biol 2001; 21(11): 1720–6PubMedCrossRef

68.

McKenna CJ, Camrud AR, Sangiorgi G, et al. Fibrin-film stenting in a porcine coronary injury model: efficacy and safety compared with uncoated stents. J Am Coll Cardiol 1998; 31(6): 1434–8PubMedCrossRef

69.

Flugelman MY, Virmani R, Leon MB, et al. Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro. Circ Res 1992; 70(2): 348–54PubMedCrossRef

70.

Sousa JE, Costa MA, Abizaid AC, et al. Sustained suppression of neointimal proliferation by sirolimus-eluting stents: one-year angiographie and intravascular ultrasound follow-up. Circulation 2001; 104(17): 2007–11PubMedCrossRef

71.

Isner JM, Walsh K, Symes J, et al. Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease. Hum Gene Ther 1996 May 20; 7(8): 959–88PubMedCrossRef

72.

Mann MJ, Whittemore AD, Donaldson MC, et al. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial. Lancet 1999; 354(9189): 1493–8PubMedCrossRef

73.

Vajanto I, Rissanen TT, Rutanen J, et al. Evaluation of angiogenesis and side effects in ishemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. J Gene Med. In press 2002, (5) 76

74.

Horowitz JR, Rivard A, van der Zee R, et al. Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension: evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol 1997; 17(11): 2793–800PubMedCrossRef

75.

Celletti FL, Waugh JM, Amabile PG, et al. Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat Med 2001; 7(4): 425–9PubMedCrossRef

76.

Celletti FL, Hilfiker PR, Ghafouri P, et al. Effect of human recombinant vascular endothelial growth factorl65 on progression of atherosclerotic plaque. J Am Coll Cardiol 2001; 37(8): 2126–30PubMedCrossRef

77.

Lehrman S. Virus treatment questioned after gene therapy death. Nature 1999; 401(6753): 517–8PubMedCrossRef

Titel: Gene Therapy for Restenosis
Current Status
verfasst von: Juha Rutanen
Johanna Markkanen
Dr Seppo Ylä-Herttuala
Publikationsdatum: 01.08.2002
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 11/2002
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200262110-00001

Springer Medizin

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