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Therapeutische Angiogenese

  • Chapter
Interventionelle Gefäßtherapie

Zusammenfassung

Die Identifizierung angiogener Wachstumsfaktoren ermöglichte die Entwicklung neuartiger Strategien zur Behandlung chronischer Gefäßverschlüsse. Die therapeutische Angiogenese könnte eine potentielle alternative Therapie für Patienten mit einer kritischen Beinischämie auf dem Boden einer Kapillaraussprossung (Angiogenese) und der Neubildung von Kollateralgefäßen (Arteriogenese) darstellen. In-vitro-und experimentelle In-vivo-Untersuchungen konnten die Wirksamkeit der vermehrten Kollateralenbildung und funktionellen Durchblutungsverbesserung bei experimenteller Beinischämie sowohl für rekombinante Gefäßwachstumsfaktoren als auch für gentherapeutische Strategien nachweisen. Gentherapeutische Strategien besitzen den Vorteil einer Minimierung systemischer Nebenwirkungen und der langsamen und kontinuierlichen Freisetzung des kodierten Faktors, was einen länger anhaltenden angiogenen Effekt er-laubt. In überwiegend unkontrollierten klini­schen-Phase-I- und -IIa-Studien wurden die Machbarkeit und die Effizienz der Gefäßbe­handlungen mit Wachstumsfaktoren gezeigt. Die Ergebnisse plazebokontrollierter, und doppel­blinder Studien sind zur sicheren Beurteilung des therapeutischen Pozentials abzuwarten.

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Literatur

  1. 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:I365–371

    Article  Google Scholar 

  2. Asahara T, Chen D, Tsurumi Y, Kearney M, Rossow S, Passeri J, Symes JF, Isner JM (1996) Accelerated restitution of endothelial integrity and endothelium-dependent function after phVEGF165 gene transfer. Circulation 94:3291–3302

    Article  PubMed  CAS  Google Scholar 

  3. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228

    Article  PubMed  CAS  Google Scholar 

  4. Baffour R, Berman J, Garb JL, Rhee SW, Kaufman J, Friedmann P (1992) 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 16:181–191

    Article  PubMed  CAS  Google Scholar 

  5. Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM (1998) Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia [see comments]. Circulation 97:1114–1123

    Article  PubMed  CAS  Google Scholar 

  6. Bauters C, Asahara T, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM (1994) Physiological assessment of augmented vascularity induced by VEGF in ischemic rabbit hindlimb. Am J Physiol 267:H1263–1271

    PubMed  CAS  Google Scholar 

  7. Brogi E, Schatteman G, Wu T, Kim EA, Varticovski L, Keyt B, Isner JM (1996) Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Invest 97:469–476

    Article  PubMed  CAS  Google Scholar 

  8. Bush RL, Pevec WC, Ndoye A, Cheung AT, Sasses J, Pearson DN (1998) Regulation of new blood vessel growth into ischemic skeletal muscle. J Vasc Surg 28:919–928

    Article  PubMed  CAS  Google Scholar 

  9. Chleboun JO, Martins RN, Mitchell CA, Chirila TV (1992) bFGF enhances the development of the collateral circulation after acute arterial occlusion. Biochem Biophys Res Commun 185:510–516

    Article  PubMed  CAS  Google Scholar 

  10. Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364

    Article  PubMed  CAS  Google Scholar 

  11. Folkman J (1971) Tumor angiogenesis: Therapeutic implications. N Engl J Med 285:1182–1186

    Article  PubMed  CAS  Google Scholar 

  12. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  PubMed  CAS  Google Scholar 

  13. Goede V, Brogelli L, Ziche M, Augustin HG (1999) Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer 82: 765–770

    Article  PubMed  CAS  Google Scholar 

  14. Harada K, Friedman M, Lopez JJ, Wang SY, Li J, Prasad PV, Pearlman JD, Edelman ER, Selike FW, Simons M (1996) Vascular endothelial growth factor administration in chronic myocardial ischemia. Am J Physiol 270:H1791–1802

    PubMed  CAS  Google Scholar 

  15. Ibukiyama C (1996) Angiogenic therapy using fibroblast growth factors and vascular endothelial growth factors for ischemic vascular lesions. Jpn Heart J 37:285–300

    Article  PubMed  CAS  Google Scholar 

  16. Inoue M, Itoh H, Ueda M, Naruko T, Kojima A, Komatsu R, Doi K, Ogawa Y, Tamura N, Takaya K, Igaki T, Yamashita J, Chun TH, Masatsugu K, Becker AE, Nakao K (1998) Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysio-logical significance of VEGF in progression of atherosclerosis. Circulation 98:2108–2116

    Article  PubMed  CAS  Google Scholar 

  17. Ischemia EWGocl (1991) Second European Con-sensus document on chronic critical leg ischemia. Circulation 84(Suppl IV):IV1–IV26

    Google Scholar 

  18. Isner JM, Asahara T (1999) Angiogenesis and vas-culogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 103:1231–1236

    Article  PubMed  CAS  Google Scholar 

  19. 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 [see comments]. Lancet 348:370–374

    Article  PubMed  CAS  Google Scholar 

  20. Isner JM, Walsh K, Symes J, Pieczek A, Takeshita S, Lowry J, Rosenfield K, Weir L, Brogi E, Jurayj D (1996) Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease. Hum Gene Ther 7:959–988

    Article  PubMed  CAS  Google Scholar 

  21. Isner JM, Baumgartner I, Rauh G, Schainfeld R, Blair R, Manor O, Razvi S, Symes JF (1998) Treat-ment of thromboangiitis obliterans (Buerger’s disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg 28:964–973

    Article  PubMed  CAS  Google Scholar 

  22. Ito WD, Arras M, Scholz D, Winkler B, Htun P, Schaper W (1997) Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion. Am J Physiol 273: H1255–1265

    PubMed  CAS  Google Scholar 

  23. Ito WD, Arras M, Winkler B, Scholz D, Schaper J, Schaper W (1997) Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion. Circ Res 80:829–837

    Article  PubMed  CAS  Google Scholar 

  24. Laitinen M, Makinen K, Manninen H, Matsi P, Kossila M, Agrawal RS, Pakkanen T, Luoma JS, Viita H, Hartikainen J, Alhava E, Laakso M, Ylä-Herttuala S (1998) Adenovirus-mediated gene transfer to lower limb artery of patients with chronic critical leg ischemia. Hum Gene Ther 9:1481–1486

    Article  PubMed  CAS  Google Scholar 

  25. Lazarous DF, Scheinowitz M, Shou M, Hodge E, Rajanayagam S, Hunsberger S, Robison WG, Jr., Stiber JA, Correa R, Epstein SE, et al. (1995) Effects of chronic systemic administration of basic fibroblast growth factor on collateral development 38. in the canine heart. Circulation 91:145–153

    Article  PubMed  CAS  Google Scholar 

  26. 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 94:1074–1082

    Article  PubMed  CAS  Google Scholar 

  27. Lazarous DF, Unger EF, Epstein SE, Stine A, Arevato JL, Quyyumi AA (1998) Effect of basic fibroblast growth factor on lower extremity blood flow in patients with intermittent claudication: preliminary results. Circulation 98:I-456

    Google Scholar 

  28. Lehrman S (1999) Virus treatment questioned after gene therapy death. Nature 401:517–518

    Article  PubMed  CAS  Google Scholar 

  29. Losordo DW, Pickering JG, Takeshita S, Leclerc G, Gal D, Weir L, Kearney M, Jekanowski J, Isner JM (1994) Use of the rabbit ear artery to serially as-sess foreign protein secretion after site-specific ar-terial gene transfer in vivo. Evidence that anatomic identification of successful gene transfer may underestimate the potential magnitude of transgene expression. Circulation 89:785–792

    CAS  Google Scholar 

  30. Makinen K, Laitinen M, Manninen H, Matsi P, Al-hava E, Ylä-Herttuala S (1999) Catheter-mediated VEGF gene transfer to human lower limb arteries after PTA. Circulation 100:I-770

    Google Scholar 

  31. Martins RN, Chleboun JO, Sellers P, Sleigh M, Muir J (1994) The role of PDGF-BB on the development of the collateral circulation after acute arterial occlusion. Growth Factors 10:299–306

    Article  PubMed  CAS  Google Scholar 

  32. Morishita R, Nakamura S, Hayashi S, Taniyama Y, Moriguchi A, Nagano T, Taiji M, Noguchi H, Takeshita S, Matsumoto K, Nakamura T, Higaki J, Ogihara T (1999) Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy. Hypertension 33:1379–1384

    Article  PubMed  CAS  Google Scholar 

  33. Nabel EG, Yang ZY, Plautz G, Forough R, Zhan X, Haudenschild CC, Maciag T, Nabel GJ (1993) Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo. Nature 362:844–846

    Article  PubMed  CAS  Google Scholar 

  34. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. Faseb J 13:9–22

    PubMed  CAS  Google Scholar 

  35. Nikol S, Engelmann MG, Armeanu S, Pelisek J, Fuchs A, Zaehringer C, Quilici J, Mesana T, Rolland PH (1999) District-specific influence of vascular endothelial growth factor 165 (VEGF-165) on coronary and peripheral arteries resulting in arteriogenesis or angiogenesis. Circulation 100:I-489

    Google Scholar 

  36. Pu LQ, Sniderman AD, Brassard R, Lachapelle KJ, Graham AM, Lisbona R, Symes JF (1993) Enhanced revascularization of the ischemic limb by angiogenic therapy. Circulation 88:208–215

    Article  PubMed  CAS  Google Scholar 

  37. Rauh G, Gravereaux E, Pieczek A, Curry C, Schainfeld R, Isner JM (1999) Assessment of safety and efficiency of intramuscular gene therapy with VEGF-2 in patients with critical limb ischemia. Circulation 100:I-770

    Google Scholar 

  38. Rivard A, Fabre JE, Silver M, Chen D, Murohara T, Kearney M, Magner M, Asahara T, Isner JM (1999) Age-dependent impairment of angiogenesis. Circulation 99:111–120

    Article  PubMed  CAS  Google Scholar 

  39. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B, Peters K, Isner JM (1999) Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol 154:355–363

    Article  PubMed  CAS  Google Scholar 

  40. Safi J, Jr., Gloe TR, Riccioni T, Kovesdi I, Capogrossi MC (1997) Gene therapy with angiogenic factors: a new potential approach to the treatment of ischemic diseases. J Mol Cell Cardiol 29:2311–2325

    Article  PubMed  CAS  Google Scholar 

  41. Schaper W (1996) Collateral vessel growth in the human heart. Role of fibroblast growth factor-2 [editorial; comment]. Circulation 94:600–601

    Article  PubMed  CAS  Google Scholar 

  42. Schaper W, Schaper J (1993) Collateral circulation: Heart, brain, kidney, limbs. Dortrecht, Netherlands: Kluwer Academic Publishers

    Book  Google Scholar 

  43. Shyu KG, Manor O, Magner M, Yancopoulos GD, Isner JM (1998) Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb. Circulation 98:2081–2087

    Article  PubMed  CAS  Google Scholar 

  44. Simovic D, Ropper AH, Isner JM, Weinberg DH (1999) Improvement in ischemic limb neuropathy after VEGF gene therapy. Circulation 100:I-770 (Abstract)

    Google Scholar 

  45. Stavri GT, Hong Y, Zachary IC, Breier G, Baskerville PA, Yla Herttuala S, Risau W, Martin JF, Erusalimsky JD (1995) Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells. FEBS Lett 358:311–315

    Article  PubMed  CAS  Google Scholar 

  46. Takeshita S, Pu LQ, Stein LA, Sniderman AD, Bunting S, Ferrara N, Isner JM, Symes JF (1994) Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation 90:228–234

    Google Scholar 

  47. Takeshita S, Zheng LP, Brogi E, Kearney M, Pu LQ, Bunting S, Ferrara N, Symes JF, Isner JM (1994) Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662–670

    Article  PubMed  CAS  Google Scholar 

  48. 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 227:628–635

    Article  PubMed  CAS  Google Scholar 

  49. Takeshita S, Isshiki T, Ochiasi M, Eto K, Mori H, Tanaka E, Umetani K, Sato T (1998) Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endthelial growth factor in a rat model of hindlimb ischemia. Circulation 98:1261–1263

    Article  PubMed  CAS  Google Scholar 

  50. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438

    Article  PubMed  CAS  Google Scholar 

  51. Tsurumi 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 94:3281–3290

    Article  PubMed  CAS  Google Scholar 

  52. Tuder RM, Flook BE, Voelkel NF (1995) Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 95:1798–1807

    Article  PubMed  CAS  Google Scholar 

  53. Van Belle E, Witzenbichler B, Chen D, Silver M, Chang L, Schwall R, Isner JM (1998) Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: the case for paracrine amplification of angiogenesis. Circulation 97:381–390

    Article  PubMed  Google Scholar 

  54. Waltenberger J (1997) Modulation of growth factor action: implications for the treatment of cardiovascular diseases. Circulation 96:4083–4094

    Article  PubMed  CAS  Google Scholar 

  55. Witzenbichler B, Asahara T, Murohara T, Silver M, Spyridopoulos I, Magner M, Principe N, Kearney M, Hu JS, Isner JM (1998) Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. Am J Pathol 153:381–394

    Article  PubMed  CAS  Google Scholar 

  56. Wolfe JH, Wyatt MG (1997) Critical and subcritical ischaemia. Eur J Vasc Endovasc Surg 13:578–582

    Article  PubMed  CAS  Google Scholar 

  57. Wunsch M, Sharma HS, Markert T, Bernotat Danielowski S, Schott RJ, Kremer P, Bleese N, Schaper W (1991) In situ localization of transforming growth factor beta 1 in porcine heart: enhanced expression after chronic coronary artery constriction. J Mol Cell Cardiol 23:1051–1062

    Article  PubMed  CAS  Google Scholar 

  58. Yla-Herttuala S, Martin JF (2000) Cardiovascular gene therapy. Lancet 355:213–222

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. M. G. Engelmann
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  2. S. Nikol
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Editor information

Editors and Affiliations

  1. Kardiologische Fachklinik Herz- und Kreislaufzentrum, Rotenburg an der Fulda, Heinz-Meise-Str. 100, Rotenburg a.d.F., 36199, Germany

    Christian Vallbracht

  2. LVA Aggertalklinik, Am Sondersiefen 18, Engelskirchen, 51766, Germany

    Franz-Josef Roth

  3. Abteilung für Angiologie, Dominikus-Krankenhaus Düsseldorf, Am Heerdter Krankenhaus 2, Düsseldorf, 40549, Germany

    Andreas L. Strauss (Chefarzt) (Chefarzt)

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Engelmann, M.G., Nikol, S. (2002). Therapeutische Angiogenese. In: Vallbracht, C., Roth, FJ., Strauss, A.L. (eds) Interventionelle Gefäßtherapie. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-642-57540-2_32

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  • DOI: https://doi.org/10.1007/978-3-642-57540-2_32

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-642-63296-9

  • Online ISBN: 978-3-642-57540-2

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