Hamostaseologie 2000; 20(04): 167-172
DOI: 10.1055/s-0037-1619488
Original article
Schattauer GmbH

Klinische Ergebnisse der Behandlung der koronaren Herzkrankheit mit Wachstumsfaktoren

Clinical results of the treatment of coronary artery disease with growth factors
Th. Hoppert
1   Klinik für Thorax-, Herz- und Gefäßchirurgie, Klinikum Fulda (Direktor: Professor Dr. Th. J. Stegmann)
,
R. Ibing
2   Medizinische Klinik I, Klinikum Fulda (Direktor: Prof. Dr. T. Bonzel)
,
A. Schneider
1   Klinik für Thorax-, Herz- und Gefäßchirurgie, Klinikum Fulda (Direktor: Professor Dr. Th. J. Stegmann)
,
M. Popp
1   Klinik für Thorax-, Herz- und Gefäßchirurgie, Klinikum Fulda (Direktor: Professor Dr. Th. J. Stegmann)
,
Th. J. Stegmann
1   Klinik für Thorax-, Herz- und Gefäßchirurgie, Klinikum Fulda (Direktor: Professor Dr. Th. J. Stegmann)
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2017 (online)

Zusammenfassung

Die aktuellen Behandlungsmethoden der koronaren Herzkrankheit zielen auf Minimierung des Infarktrisikos und Reduktion der Symptome durch Senkung des myokardialen Sauerstoffbedarfs, durch Verbesserung der myokardialen Perfusion sowohl medikamentös als auch mechanisch durch PTCA oder Bypasschirurgie und durch Prävention einer weiteren Progression der Erkrankung. Trotz des hohen technischen Standards der interventionellen oder operativen Verfahren der myokardialen Revaskularisation sind diese bei Patienten mit diffuser Arteriosklerose und peripherem Gefäßbefall nicht anwendbar. Die Induktion der Angiogenese durch humane angiogenetische Wachstumsfaktoren entwickelt sich speziell bei dieser Patientengruppe zu einer neuen Therapiemodalität und stellt neben medikamentöser Therapie, PTCA und Bypasschirurgie ein viertes, neuartiges Behandlungsprinzip der koronaren Herzkrankheit dar. »Polypeptide Fibroblast Growth Factor« (FGF) und »Vascular Endothelial Growth Factor« (VEGF) scheinen einen besonders starken Effekt im Hinblick auf die Induktion der Angiogenese im hypoxischen Gewebe auszuüben.

Summary

Currently available approaches for treating coronary heart disease aim to relieve symptoms and the risk of myocardial infarction by reducing myocardial oxygen demand, increasing myocardial perfusion pharmcologically or mechanically by angioplasty or bypass surgery and by preventing further progression of the disease. Despite the high technical standarts of bypass surgery and interventional procedures, patients with diffuse atherosclerosis are not amenable to these techniques. Therapeuthic induction of angiogenesis by human angiogenic growth factors is evolving to be a fourth, new principle of treatment of atherosclerotic cardiovascular disease, especially for this group of patients. The polypeptides fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) seem to be powerful stimulators of angiogenesis in hypoxic tissue.

 
  • Literatur

  • 1 Baird A, Bohlen P, Esch F. et al. Acidic fibroblast growth factor (FGF) from bovine brain: amino-terminal sequence and comparison with basic FGF. EMBO J 1985; 4: 1951-6.
  • 2 Battler A, Scheinowitz M, Bor A. et al. Intracoronary injection of basic fibroblast growth factor enhances angiogenesis in infarcted swine myocardium. J Am Coll Cardiol 1993; 22: 2001-6.
  • 3 Baumgartner J, Pieczek A, Manor O. et al. Constitutive expression of ph VEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischaemia. Circulation 1998; 97: 1114-23.
  • 4 Burgess WH, Mehrman T, Friesel R. et al. Multiple forms of endothelial cell growth factor. Rapid isolation and biological and chemical characterization. J Biol Chem 1985; 260: 11389-92.
  • 5 Carmeliet P. et al. Abnormal blood vessel development and lethality in embryos lackings a single VEGF allele. Nature 1996; 380: 435-9.
  • 6 Cuevas P, Gonzalez AM, Carceller F, Baird A. Vascular response to basic fibroblast growth factor when infused onto the normal adventita or into the injured media of the rat carotid artery. Circulation Res 1991; 69: 360-9.
  • 7 Fasol R, Schumacher B, Schlaudraff K. et al. Experimental use of a modified fibrin-glue to induce site-directed angiogenesis from the aorta to the heart. J Thorac Cardiovasc Surg 1994; 107: 1432-9.
  • 8 Ferrara N, Carrer-Moore K, Chen H. et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439-42.
  • 9 Folkman J. Tumour angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182-6.
  • 10 Folkman J, Klagsbrun M. Angiogenic factors. Science 1987; 235: 442-7.
  • 11 Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992; 267: 10931-4.
  • 12 Folkman J. Clinical applications of research on angiogenesis. N Engl J Med 1995; 333: 1757-63.
  • 13 Friesel R, Burgess WH, Mehrman T. et al. The characterization of the receptor for endothelial cell growth factor by covalent ligand attachment. J Biol Chem 1986; 261: 7581-4.
  • 14 Harada K, Grossman W, Friedman M. et al. Basic fibroblast growth factor improves myocardial function in chronically ischaemic porcine hearts. J Clin Invest 1994; 94: 623-30.
  • 15 Inoùe M, Hiroshi I, Ueda M. et al. Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions. Circulation 1998; 98: 2108-16.
  • 16 Isner JM, Pieczek A, Schainfeld R. et al. Clinical evidence of angiogenesis after arterial gene transfer of ph VEGF165 in patient with ischaemic limb. Lancet 1996; 348: 370-4.
  • 17 Kuzuya M, Satake S, Esaki T. et al. Induction of angiogenesis by smooth muscle cell-derived factor: possible role in neovascularization in atherosclerotic plaque. J Cell Physiol 1995; 164: 658-67.
  • 18 Laham RJ, Sellke FW, Edelman ER. et al. Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery. Circulation 1999; 100: 1865-71.
  • 19 Losordo DW, Vale PR, Symes JF. et al. Gene therapy for myocardial angiogenesis. Initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischaemia. Circulation 1998; 98: 2800-4.
  • 20 Lazarous DF, Scheinowitz M, Shou M. et al. Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury. Circulation 1996; 94: 1074-82.
  • 21 Maciag T, Mehrman T, Friesel R. et al. Heparin binds endothelial cell growth factor, the principal mitogen in the bovine brain. Science 1984; 225: 932-5.
  • 22 Nabel EG, Yang ZY, Plautz G. et al. Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo. Nature 1993; 362: 844-6.
  • 23 Nomura M, Yamagishi S, Havada S. et al. Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxiainduced proliferation of endothelial cells and pericytes. J Biol Chem 1995; 270: 28316-24.
  • 24 Risau W, Flamme I. Vasculogenesis. Ann Rev Cell Dev Biol 1995; 11: 79-91.
  • 25 Rosengart TK, Lee LY, Patel SR. et al. Angiogenesis gene therapy. Circulation 1999; 100: 468-74.
  • 26 Schaper W, Ito W. Molecular mechanisms of collateral vessel growth. Circ Res 1996; 79: 911-9.
  • 27 Schlaudraff K, Schumacher B, von Specht BU. et al. Growth of “new” coronary vascular structures by angiogenetic growth factors. Eur J Cardiothorac Surg 1993; 7: 637-44.
  • 28 Schumacher B, Pecher P, von Specht BU. et al. Induction of neoangiogenesis in ischaemic myocardium by human growth factors. First clinical results of a new treatment of coronary heart disease. Circulation 1998; 97: 645-50.
  • 29 Schumacher B, Stegmann T, Pecher P. The stimulation of neoangiogenesis in the ischaemic human heart by the growth factor FGF: first clinical results. J Cardiovasc Surg 1998; 39: 783-9.
  • 30 Sellke FW, Wang SY, Stamler A. et al. Angiogenesis induced by acidic fibroblast growth factor as an alternative method of revascularization for chronic myocardial ischaemia. Surgery 1996; 120: 182-8.
  • 31 Shing Y, Folkman J, Sullivan R. et al. Heparin affinity: purification of a tumour-derived capillary endothelial cell growth factor. Science 1984; 223: 1296-8.
  • 32 Stegmann TJ. FGF-1: a human growth factor in the induction of neoangiogenesis. Exp Opin Invest Drugs 1998; 7: 2011-5.
  • 33 Stegmann TJ. New approaches to coronary heart disease: Induction of neovascularization by growth factors. BioDrugs 1999; 11: 301-8.
  • 34 Stegmann TJ, Hoppert T. Combined local angiogenesis and surgical revascularization for coronary artery disease. Current Intervent Cardiol Reports 1999; 1: 172-8.
  • 35 Stegmann TJ. Intramyocardial injection of acidic fibroblast growth factor: adjunct to bypass surgery and monotherapy for coronary heart disease. In: Kornowski R, Epstein SE, Leon MB. (Hrsg). Handbook of Myocardial Revascularization and Angiogenesis. London: M. Dunitz Ltd; 2000: 201-14.
  • 36 Stegmann TJ, Hoppert T, Schlürmann W, Gemeinhardt S. First angiogenic treatment of coronary heart disease by FGF-1: Long-term results after three years. J Cardiac Vascular Regeneration 2000; 1: 5-10.
  • 37 Thomas KA. Vascular endothelial growth factor, a potent and selective angiogenetic agent. J Biol Chem 1996; 271: 603-6.
  • 38 Thompson JA, Haudenschild CC, Anderson KD. et al. Heparin-binding growth factor induces the formation of organoid neovascular structures in vivo. Proc Natl Acad Sci USA 1989; 86: 7928-32.
  • 39 Tudor RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDT/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 1995; 95: 1798-807.
  • 40 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: 1588-95.
  • 41 Ware JA, Simons M. Angiogenesis in ischaemic heart disease. Nat Med 1997; 3: 158-64.
  • 42 Yanagisawa-Miwa A, Uchida Y, Nakamura F. et al. Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. Science 1992; 257: 1401-2.