Skip to main content
SpringerLink
Log in

Vaskulärer endothelialer Wachstumsfaktor (VEGF): Therapeutische Angiogenese und Vaskulogenese in der Behandlung kardiovaskulärer Erkrankungen

Vascular endothelial growth factor (VEGF): Therapeutic angiogenesis and vasculogenesis in the treatment of cardiovascular disease

  • Published:
Medizinische Klinik Aims and scope Submit manuscript

Zusammenfassung

Die Bildung neuer Blutgefäße ist bei einer Vielzahl von physiologischen Vorgängen, wie zum Beispiel der Embryogenese und dem weiblichen Reproduktionszyklus, sowie bei pathologischen Prozessen, wie zum Beispiel dem Tumorwachstum, der Wundheilung und der Neovaskularisation ischämischer Gewebe, von Bedeutung. Vaskulogenese und Angiogenese sind die Mechanismen, die für die Neubildung von Gefäßen verantwortlich sind. Während die Angiogenese die Neubildung von Gefäßen aus vorbestehenden Kapillaren im Embryo und im erwachsenen Organismus beschreibt, schien die Vaskulogenese, die Gefäßneubildung aus in situ differenzierenden Endothelvorläuferzellen, bislang auf die Embryogenese beschränkt zu sein. Neueste Ergebnisse zeigen jedoch, daß aus dem Knochenmark stammende endotheliale Vorläuferzellen in der erwachsenen Spezies im peripheren Blut nachweisbar und an der Neovaskularisation beteiligt sind. Molekular- und zellbiologische Untersuchungen deuten daraufhin, daß verschiedene Zytokine und Wachstumsfaktoren stimulierend auf die Mobilisierung dieser endothelialen Vorläuferzellen aus dem Knochenmark wirken.

Die Ergebnisse mit GM-CSF (granulocyte macrophage-colony stimulating factor) und VEGF (vascular endothelial growth factor) eröffnen eine neue Betrachtungsweise für die klinische Verwendung von Zytokinen und vor allem für den Einsatz gentherapeutisch anwendbarer Wachstumsfaktoren. Exogen als Protein zugeführte oder als Plasmid-DNS kodierte Wachstumsfaktoren können nicht nur auf dem Wege der Angiogenese, sondern auch unter Mobilisierung von Endothelvorläuferzellen an der Neovaskularisation beteiligt sein.

Abstract

The formation of new blood vessel is essential for a variety of physiological processes like embryogenesis and the female reproduction as well as pathological processes like tumor growth, wound healing and neovascularization of ischemic tissue. Vasculogenesis and angiogenesis are the mechanisms responsible for the development of the blood vessels. While angiogenesis refers to the formation of capillaries from pre-existing vessels in the embryo and adult organism, vasculogenesis, the development of new blood vessels from in situ differentiating endothelial cells, has been previously considered restricted to embryogenesis. Recent investigations, however, show the existence of endothelial progenitor cells (EPCs) in the peripheral blood of the adult and their participation in ongoing neovascularization. Molecular and cell-biological experiments suggest that different cytokines and growth factors have a stimulatory effect on these bone-marrow derived EPCs.

Results with GM-CSF (granulocyte macrophage-colony stimulating factor) and VEGF (vascular endothelial growth factor) open a new insight into the clinical use of cytokines and in particular the use of growth factors in gene therapy. The administration via protein or plasmid-DNA for neovascularization seems to enhance both pathways, angiogenesis and vasculogenesis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Asahara T, Bauters C, Zheng LP, et al. Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 1995;92:II-365–71.

    CAS  Google Scholar 

  2. Asahara T, Masuda H, Takahashi T, et al. Bone-marrow derived endothelial progenitor cells contribute to postnatal vasculogenesis. Circulation (submitted for publication).

  3. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:965–7.

    Article  Google Scholar 

  4. Asahara T, Takahashi T, Isner J. Endothelial progenitor cell for post-natal neovascularization. Cardiovasc Res Update 1998;16:605–17.

    CAS  Google Scholar 

  5. Asahara T, Takahashi T, Kalka C, et al. A novel function for VEGF: mobilization of bone marrow-derived endothelial progenitor cells. Circulation 1998;98:1–605.

    Google Scholar 

  6. Ausprunk DH, Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 1977;14:53–65.

    Article  PubMed  CAS  Google Scholar 

  7. 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;16:181–91.

    Article  PubMed  CAS  Google Scholar 

  8. Barleon B, Sozzani S, Zhou D, Weich H, Montovani A, Marme D. Migration of human monocytes in response to vascular endothelial growth factor is mediated via the VEGF receptor flt-1. Blood 1996;97:3336–43.

    Google Scholar 

  9. 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;97:1114–23.

    PubMed  CAS  Google Scholar 

  10. Brogi E, Schatteman G, Wu T, et al. Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Invest 1996;96:169–76.

    Google Scholar 

  11. Brown LF, Detmar M, Claffey K, et al. Vascular permeability factor/vascular endothelial growth factor. A multifunctional angiogenic cytokine. In: Goldberg RE, ed. Regulation of angiogenesis. Basel: Birkhäuser, 1997; 233–73.

    Google Scholar 

  12. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380:435–9.

    Article  PubMed  CAS  Google Scholar 

  13. Connolly DT, Hewelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 1989;84:1470–8.

    Article  PubMed  CAS  Google Scholar 

  14. D’Amore PA, Thompson RW. Mechanisms of angiogenesis. Annu Rev Physiol 1987;49:453–64.

    Article  PubMed  Google Scholar 

  15. De Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992;255:989–91.

    Article  PubMed  Google Scholar 

  16. Dormandy J, Mahir M, Ascady G, et al. Fate of the patient with chronic leg ischaemia. J Cardiovasc Surg 1989;1:50–7.

    Google Scholar 

  17. Dumont DJ, Yamaguchi TP, Conlon RA, Rossant J, Breitman ML. tec, a novel tyrosine kinase gene located on mouse chromosome-4, is expressed in endothelial cells and their presumptive precursors. Oncogene 1992;7:1471–80.

    PubMed  CAS  Google Scholar 

  18. European Working Group on Critical Leg I. Second European consensus document on chronic critical leg ischemia. Circulation 1991;84:IV-1–26.

    Google Scholar 

  19. Ferrara N. Vascular endothelial growth factor. Trends Cardiovasc Med 1993;3:244–50.

    Article  CAS  Google Scholar 

  20. Ferrara N, Carver-Moore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996;380:439–42.

    Article  PubMed  CAS  Google Scholar 

  21. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161:851–5.

    Article  PubMed  CAS  Google Scholar 

  22. Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992;13:18–32.

    PubMed  CAS  Google Scholar 

  23. Fina J, Molgard HV, Robertson D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood 1990;75:2417–26.

    PubMed  CAS  Google Scholar 

  24. Flamme I, Risau W. Induction of vasculogenesis and hemotopoiesis in vitro. Development 1992;116:435–9.

    PubMed  CAS  Google Scholar 

  25. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–6.

    PubMed  CAS  Google Scholar 

  26. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med 1995;1:27–31.

    Article  PubMed  CAS  Google Scholar 

  27. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931–4.

    PubMed  CAS  Google Scholar 

  28. Fong GH, Rossant J, Gersenstein M, Breitman ML. Role of the Flt-I receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376:66–70.

    Article  PubMed  CAS  Google Scholar 

  29. Gilbert SF. Developmental biology, 4th edn. Sunderland, MA: Sinauer Associates, Inc., 1997:342.

    Google Scholar 

  30. Goldberg MA, Schneider TJ. Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem 1994;269:4355–9.

    PubMed  CAS  Google Scholar 

  31. His W. Leoithoblast und Angioblast der Wirbeltiere. Abhandl K S Ges Wiss Math Ohys 1900;22:171–328.

    Google Scholar 

  32. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992;267:26031–7.

    PubMed  CAS  Google Scholar 

  33. Ikeda E, Achen MG, Breir G, Risau W. Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 Glioma cells. J Biol Chem 1995;270:19761–6.

    Article  PubMed  CAS  Google Scholar 

  34. Isner JM, Asahara T. Therapeutic angiogenesis. Front Biosci 1998;3:e49–69.

    PubMed  CAS  Google Scholar 

  35. Isner JM, Feldman L. Gene therapy for arterial disease. Lancet 1994;344:1653–4.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

  37. Isner JM, Rosenfield K. Redefining the treatment of peripheral artery disease: role of percutaneous revascularization. Circulation 1993;88:1534–57.

    PubMed  CAS  Google Scholar 

  38. Isner JM, Walsh K, Symes JF, et al. Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery disease. Circulation 1995;91:2687–92.

    PubMed  CAS  Google Scholar 

  39. Jakeman LB, Winer J, Bennett GL, Altar CA, Ferrara N. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992;89:244–53.

    Article  PubMed  CAS  Google Scholar 

  40. Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 1996;15:290–8.

    PubMed  CAS  Google Scholar 

  41. Jussila L, Valtola R, Partanen TA, et al. Lymphatic endothelium and Kaposi’s sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res 1998;58:1599–604.

    PubMed  CAS  Google Scholar 

  42. Kalka C, Masuda H, Takahashi T, Li T, Asahara T. Administration of culture-expanded endothelial progenitor cells (EPC) augments therapeutic neovascularization. Circulation 1998;98:I-455.

    Google Scholar 

  43. Kalka C, Takahashi T, Masuda H, Pieczek A, Asahara T. Intramuscular VEGF gene transfer mobilizes endothelial progenitor cells in human subjects. Circulation 1998;98:I-322.

    Google Scholar 

  44. Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989;246:1309–12.

    Article  PubMed  CAS  Google Scholar 

  45. Klagsbrun M, D’Amore PA. Regulators of angiogenesis. Annu Rev Physiol 1991;53:217–39.

    Article  PubMed  CAS  Google Scholar 

  46. Ledney GD, Stewart DA, Gruber DF, Gelston HM Jr, Exum ED, Sheehy PA. Hematopoietic colony-forming cells from mice after wound trauma. J Surg Res 1985; 38:55–65.

    Article  PubMed  CAS  Google Scholar 

  47. Levy AP, Tamargo R, Brem H, Nathans D. An endothelial cell growth factor from the mouse neuroblastoma cell line NB41. Growth Factors 1989;2:9–19.

    Article  PubMed  CAS  Google Scholar 

  48. 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 ischemia. Circulation 1998;98:2800–4.

    PubMed  CAS  Google Scholar 

  49. Matthews W, Jordan CT, Gavin M, Jenkins NA, Copeland NG, Lemischka IR. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Proc Natl Acad Sci U S A 1991;88:9026–30.

    Article  PubMed  CAS  Google Scholar 

  50. Millauer B, Wizigmann-Voos S, Schnurch H, et al. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 1993;72:835–46.

    Article  PubMed  CAS  Google Scholar 

  51. 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.

    Article  PubMed  CAS  Google Scholar 

  52. Nicosia RF, Nicosia SV, Smith M. Vascular endothelial growth factor, platelet-derived growth factor, and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am J Pathol 1994;145:1023–9.

    PubMed  CAS  Google Scholar 

  53. Nishikawa SI, Nishikawa S, Hirashima M, Matsuyoshi N, Kodama H. Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages. Development 1998;125:1747–57.

    PubMed  CAS  Google Scholar 

  54. Ogawa S, Oku A, Sawano A, Yamaguchi S, Yazaki Y, Shibuya M. A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J Biol Chem 1998;273:31273–82.

    Article  PubMed  CAS  Google Scholar 

  55. Olander JV, Connolly DT, DeLarco JE. Specific binding of vascular permeability factor to endothelial cells. Biochem Biophys Res Commun 1991;175:68–76.

    Article  PubMed  CAS  Google Scholar 

  56. Olofsson B, Pajusoka K, Kaipainen A, et al. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci U S A 1996;93:2576–81.

    Article  PubMed  CAS  Google Scholar 

  57. Pardanaud L, Yassme F, Dieterlen-Lievre F. Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny. Development 1989;105:473–85.

    PubMed  CAS  Google Scholar 

  58. Park JE, Chen HH, Winer J, Houck KA, Ferrara N Placenta growth factor: potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 1994;269:25646–54.

    PubMed  CAS  Google Scholar 

  59. Plouet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 1989;8:3801–6.

    PubMed  CAS  Google Scholar 

  60. Pu LQ, Sniderman AD, Brassard R, et al. Enhanced revascularization of the ischemic limb by means of angiogenic therapy. Circulation 1993;88:208–15.

    PubMed  CAS  Google Scholar 

  61. Quinn TP, Peters KG, De VC, Ferrara N, Williams LT. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A 1993;90:7533–7.

    Article  PubMed  CAS  Google Scholar 

  62. Risau W. Differentiation of endothelium. FASEB J 1995;9:926–33.

    PubMed  CAS  Google Scholar 

  63. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol 1995;11:73–91.

    Article  PubMed  CAS  Google Scholar 

  64. Risau W, Sariola H, Zerwes H-G, et al. Vasculogenesis and angiogenesis in embryonic stem cell-derived embryoid bodies. Development 1988;102:471–8.

    PubMed  CAS  Google Scholar 

  65. Schumacher B, Pecher P, Specht BU von, 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;97:645–50.

    PubMed  CAS  Google Scholar 

  66. Seetharam L, Gotoh N, Maru Y, Neufeld G, Yamaguchi S, Shibuya M. A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene 1995;10:135–47.

    PubMed  CAS  Google Scholar 

  67. Shalaby F, Ho J, Stanford WL, et al. A requirement for flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997;89:981–90.

    Article  PubMed  CAS  Google Scholar 

  68. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1 deficient mice. Nature 1995;376:62–6.

    Article  PubMed  CAS  Google Scholar 

  69. Shing Y, Folkman J, Sullivan J, Butterfield R, Murray J, Klagsbrun M. Heparin-affinity purification of a tumor-derived capillary endothelial cell growth factor. Science 1984;223:1296–9.

    Article  PubMed  CAS  Google Scholar 

  70. Sholley MM, Ferguson GP, Seibel HR, Montour JL, Wilson JD. Mechanisms of neovascularization; vascular sprouting can occur without proliferation of endothelial cells. Lab Invest 1984;51:624–34.

    PubMed  CAS  Google Scholar 

  71. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992;359:843–5.

    Article  PubMed  CAS  Google Scholar 

  72. Spyridopoulos I, Brogi E, Kearney M, et al. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals. J Mol Cell Cardiol 1997;29:1321–30.

    Article  PubMed  CAS  Google Scholar 

  73. 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;91:1981–7.

    Google Scholar 

  74. Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nature Med 1999; in press.

  75. 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 

  76. Takeshita S, Zheng LP, Brogi E, et al. Therapeutic angiogenesis: a single intra-arterial bolus of vascular endothelial growth factor augments revascularisation in a rabbit ischemic hindlimb model. J Clin Invest 1994;93:662–70.

    Article  PubMed  CAS  Google Scholar 

  77. Taylor LM Jr, Porter JM. Natural history and non-operative treatment of chronic lower extremity ischemia. Philadelphia: Saunders, 1989:656–60.

    Google Scholar 

  78. Terman BI, Dougher-Vermazen M, Carrion ME, et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 1992;187:1579–86.

    Article  PubMed  CAS  Google Scholar 

  79. Thompson JA, Anderson KD, DiPietro JM. Site-directed neovessel formation in vivo. Science 1988;241:1349–52.

    Article  PubMed  CAS  Google Scholar 

  80. Tischer E, Mitchell R, Hartmann T, et al. The human gene for vascular endothelial growth factor: multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991;266:11947–54.

    PubMed  CAS  Google Scholar 

  81. 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;94:3281–90.

    PubMed  CAS  Google Scholar 

  82. Vittet D, Prandini MH, Berthier R, et al. Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood 1996;88:3424–31.

    PubMed  CAS  Google Scholar 

  83. Wang GL, Semenza GL. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA 1993;90:4304–8.

    Article  PubMed  CAS  Google Scholar 

  84. Weiss M, Orkin SH. In-vitro differentiation of murine embryonic stem cells: new approaches to old problems. J Clin Invest 1996;97:591–5.

    Article  PubMed  CAS  Google Scholar 

  85. Witzenbichler B, Van Belle E, Chang L, Schwall R. Scatter factor (SF) induces vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMC) and acts synergistic to VEGF on endothelial cell (EC) migration in vitro. Circulation 1996;94:I-593–4.

    Google Scholar 

  86. Wolfe JHN. Defining the outcome of critical ischemia: a one-year prospective study. Br J Surg 1986;73:321–8.

    Article  Google Scholar 

  87. Yamada Y, Nezu J, Shimane M, Hirata Y. Molecular cloning of a novel vascular endothelial growth factor, VEGFD. Genomics 1997;42:483–8.

    Article  PubMed  CAS  Google Scholar 

  88. Yamaguchi TP, Dumont DJ, Conlon RA, Breitman ML, Rossant J. flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 1993;118:489–98.

    PubMed  CAS  Google Scholar 

  89. Yanagisawa-Miwa A, Uchida Y, Nakamura F, et al. Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. Science 1992;257:1401–3.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Vascular Medicine, St. Elizabeth’s Medical Center, Tufts University School of Medicine, 736 Cambridge Street, 02135, Boston, MA, USA

    Christoph Kalka, Tomono Takahashi, Harushika Masuda, Takayuki Asahara & Jeffrey M. Isner

Authors
  1. Christoph Kalka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomono Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harushika Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takayuki Asahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeffrey M. Isner
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalka, C., Takahashi, T., Masuda, H. et al. Vaskulärer endothelialer Wachstumsfaktor (VEGF): Therapeutische Angiogenese und Vaskulogenese in der Behandlung kardiovaskulärer Erkrankungen. Med Klin 94, 193–201 (1999). https://doi.org/10.1007/BF03044854

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03044854

Schlüsselwörter

Key Words

Search

Navigation