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Cardiovascular Specific Gene Expression pp 179–191Cite as

Receptor Tyrosine Kinase Signaling in Vasculogenesis and Angiogenesis

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Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 214))

Abstract

The formation of the vascular system is an important process during embryonic development and several pathological situations. Knowledge of the molecular mechanisms may lead to the development of therapies for pathological processes involving both endothelial cell proliferation and new blood vessel formation as well as those characterized by insufficient nutrient and oxygen supply of tissues. An example for abnormal vessel growth are solid tumors, whose unlimited growth is absolutely dependent on the formation of new vessels. The tumor vasculature allows for nutrient supply and the formation of metastases [1]. Of similar negative influence is vessel growth in several non neoplastic conditions like rheumathoid arthritis, diabetic retinopathy and psoriasis [2,3]. In contrast, the growth of new vessels during collateral formation in the ischemic limb or the ischemic heart would be highly desirable [4,5]. The formation of the vascular system starts early in embryonic development with the generation of a primitive vascular plexus in the yolk sac by a process termed vasculogenesis [6]. It describes the fusion of endothelial cell precursors called angioblasts that have differentiated from mesodermal cells. While most organs of endodermal origin like the lung are vascularized by vasculogenesis, tissues of mesodermal and ectodermal origin like the kidney and brain are thought to be vascularized mostly by a different process called angiogenesis [7]. Angiogenesis is the generation of new vessels by budding and sprouting from already formed vessels or by subdivision of larger vessels (also called non-sprouting angiogenesis or intussusception). The newly formed vascular system is then reorganized by complex and poorly understood processes according to the tissue requirements. Tissue oxygen as well as glucose concentration are important regulators as low tissue levels induce the expression of factors that can induce vessel growth. The reorganization includes not only the formation of additional vessels but also the removal of excessive vessels, called pruning. The mediators of vessel regression are not known. Also, there is no direct evidence for programmed cell death (apoptosis) of endothelial cells during embryonic development. This may reflect either the limitations of the methodology applied or the rapid disappearance of apoptotic cells [8]. However, at least during certain phases endothelial cells seem to be dependent on survival factors [9].

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References

  1. Folkman J. Tumor angiogenesis. Adv Cancer Res 1985; 43: 175–203.

    Article  PubMed  CAS  Google Scholar 

  2. Adamis AP, Miller JW, Bernal MT, D’Amico DJ, Folkman J, Yeo TK, Yeo KT. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalm 1994; 118: 445–50.

    CAS  Google Scholar 

  3. Peacock DJ, Banquerigo ML, Brahn E. Angiogenesis inhibition supresses collagen arthritis. J Exp Med 1992; 175: 1135–38.

    Article  PubMed  CAS  Google Scholar 

  4. Colville-Nash PR, Willoughby DA. Growth factors in angiogenesis: current interest and therapeutic potential. Mol Med Today 1997;vol:14–23.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Pardanaud L, Yassine F, Dieterlen-Lièvre F. Relationship between vasculogenesis, angiogenesis and hemopoiesis during avian ontogeny. Development 1989; 105: 473–85.

    PubMed  CAS  Google Scholar 

  8. Augustin HG, Braun K, Telemenakis I, Modlich U, Kuhn W. Ovarian angiogenesis–phenotypic characterization of endothelial-cells in a physiological model of blood-vessel growth and regression. Am J Pathol 1995; 147: 339–51.

    PubMed  CAS  Google Scholar 

  9. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet S. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for rethinopathy of prematurity. Nat Med 1995; 1: 1024–28.

    Article  PubMed  CAS  Google Scholar 

  10. Franke RP, Grafe M, Schnittler H, Seiffge D, Mittermayer C, Drenckhahn D. Induction of human vascular endothelial stress fibres by fluid shear stress. Nature 1984; 307: 648–49.

    Article  PubMed  CAS  Google Scholar 

  11. Resnick N, Gimbrone MA. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J 1995; 9: 874–82.

    PubMed  CAS  Google Scholar 

  12. Millauer B, Longhi MP, Plate KH, Shawver LH, Risau W, Ullrich A, Strawn LM. Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. Cancer Res 1996; 56: 1615–20.

    PubMed  CAS  Google Scholar 

  13. Lin P, Polverini P, Dewhirst M, Shan S, Rao PS, Peters K. Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest 1997; 100: 2072–78.

    Article  PubMed  CAS  Google Scholar 

  14. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-l -deficient mice. Nature 1995; 376: 62–66.

    Article  PubMed  CAS  Google Scholar 

  15. Shalaby F, Ho J, Stanford WL, Fischer KD, Schuh AC, Schwartz L, Bernstein A, Rossant J. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997; 89: 981–90.

    Article  PubMed  CAS  Google Scholar 

  16. Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376: 66–70.

    Article  PubMed  CAS  Google Scholar 

  17. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435–39.

    Article  PubMed  CAS  Google Scholar 

  18. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea K, Powell-Braxton L, Hillan KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439–42.

    Article  PubMed  CAS  Google Scholar 

  19. Breier G, Clauss M, Risau W. Coordinate expression of vascular endothelial growth factor receptor-1 (flt-1) and its ligand suggests a paracrine regulation of murine vascular development. Dev Dynamics 1995; 204: 228–39.

    Article  CAS  Google Scholar 

  20. Stone J, Itin A, Alon T, Peer J, Gnessin H, Chang-Ling T, Keshet E. Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 1995; 15: 4738–47.

    PubMed  CAS  Google Scholar 

  21. Flamme I, von Reutern M, Drexler HCA. Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Dev Biol 1995; 171: 399–414.

    Article  PubMed  CAS  Google Scholar 

  22. Drake CJ, Little CD. Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization. Proc Natl Acad Sci USA 1995; 92: 7657–61.

    Article  PubMed  CAS  Google Scholar 

  23. Dumont DJ, Yamaguchi TP, Conlon RA, Rossant J, Breitman ML. Tek, 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 

  24. Runting AS, Stacker SA, Wilks AF. Tie2, a putative protein tyrosine kinase from a new class of cell surface receptor. Growth Factors 1993; 9: 99–105.

    PubMed  CAS  Google Scholar 

  25. Schnürch H, Risau W. Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage. Development 1993; 119: 957–68.

    PubMed  Google Scholar 

  26. Sato TN, Qin Y, Kozak CA, Audus KL. Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system. Proc Natl Acad Sci USA 1993; 90: 9355–58.

    Article  PubMed  CAS  Google Scholar 

  27. Ziegler SF, Bird TA, Schneringer JA, Schooley KA, Baum PR. Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta. Oncogene 1993; 8: 663–70.

    PubMed  Google Scholar 

  28. Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 1995; 376: 70–74.

    Article  PubMed  CAS  Google Scholar 

  29. Puri MC, Rossant J, Alitalo K, Bernstein A, Partanen J. The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBO J 1995; 14: 5884–91.

    PubMed  CAS  Google Scholar 

  30. Partanen J, Puri MC, Schwartz L, Fischer KD, Bernstein A, Rossant J. Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development. Development 1996; 122: 3013–21.

    PubMed  CAS  Google Scholar 

  31. Hashiyama M, Iwama A, Ohshiro K, Kurozumi K, Yasunaga K, Shimizu Y, Masuho Y, Matsuda I, Yamaguchi N, Suda T. Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem cells and B cells. Blood 1996; 87: 93–101.

    PubMed  CAS  Google Scholar 

  32. Batard P, Sansilvestri P, Scheinecker C, Knapp W, Debili N, Vainchenker W, Buhring HJ, Monier MN, Kukk E, Partanen J, Matikainen MT, Alitalo R, Hatzfeld J, Alitalo K. The Tie receptor tyrosine kinase is expressed by human hematopoietic progenitor cells and by a subset of megakaryocytic cells. Blood 1996; 87: 2212–20.

    PubMed  CAS  Google Scholar 

  33. Rodewald HR, Sato TN. Tiel, a receptor tyrosine kinase essential for vascular endothelial cell integrity, is not critical for the development of hematopoietic cells. Oncogene 1996; 12: 397–404.

    PubMed  CAS  Google Scholar 

  34. Dumont DJ, Fong GH, Puri MC, Gradwohl G, Alitalo K, Breitman ML. Vascularization of the mouse embryo–a study of flk-1, tek, tie, and vascular endothelial growth factor expression during development. Dev Dynam 1995; 203: 80–92.

    Article  CAS  Google Scholar 

  35. Dumont DJ, Gradwohl G, Fong GH, Puri MC, Gertsenstein M, Auerbach A, Breitman ML. Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Develop 1994; 8: 1897–909.

    Article  PubMed  CAS  Google Scholar 

  36. Saccani G, Gherardi S, Trifiro A, Bordini CS, Calza M, Freddi C. Use of ion chromatography for the measurement of organic acids in fruit juices. Journal of Chromatography 1995; 706: 395–403.

    Article  CAS  Google Scholar 

  37. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski J, Maisonpierre PC, Yancopoulos GD. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 1996; 87: 1161–69.

    Article  PubMed  CAS  Google Scholar 

  38. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997; 277: 55–60.

    Article  PubMed  CAS  Google Scholar 

  39. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996; 87: 1171–80.

    Article  PubMed  CAS  Google Scholar 

  40. 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 

  41. Cunningham SA, Arrate MP, Brock TA, Waxham MN. Interactions of Flt-1 and KDR with phospholipase C gamma–identification of the phosphotyrosine binding sites. Bioch Bioph Res Comm 1997; 240: 635–39.

    Article  CAS  Google Scholar 

  42. Cunningham SA, Waxham MN, Arrate PM, Brock TA. Interaction of the Flt-1 tyrosine kinase receptor with the p85 subunit of phosphatidytinositol 3-kinase. Mapping of a novel site involved in binding. J Biol Chem 1995; 270: 20254–57.

    Article  PubMed  CAS  Google Scholar 

  43. Waltenberger J, Claesson Welsh L, Siegbahn A, Shibuya M, Heldin CH. Different signal transduction properties of KDR and Fltl, two receptors for vascular endothelial growth factor. J Biol Chem 1994; 269: 26988–95.

    PubMed  CAS  Google Scholar 

  44. Kroll J, Waltenberger J. The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells. J Biol Chem 1997; 272: 32521–27.

    Article  PubMed  CAS  Google Scholar 

  45. Huang L, Turck CW, Rao P, Peters KG. GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase. Oncogene 1995; 11: 2097–103.

    PubMed  CAS  Google Scholar 

  46. Wang LC, Kuo F, Fujiwara Y, Gilliland DG, Golub TR, Orkin SH. Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL. EMBO J 1997; 16: 4374–83.

    Article  PubMed  CAS  Google Scholar 

  47. Kuo CT, Veselits ML, Barton KP, Lu MM, Clendenin C, Leiden JM. The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Gene Dev 1997; 11: 2996–3006.

    Article  PubMed  CAS  Google Scholar 

  48. Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA 1996; 93: 2576–81.

    Article  PubMed  CAS  Google Scholar 

  49. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K. 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: 290–98.

    PubMed  CAS  Google Scholar 

  50. Achen MG, Jeltsch M, Kukk E, MókinenE, Vitali A, Wilks AF, Alitalo K, Stacker SA. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flkl) and VEGF receptor 3 (FIt4). Proc Natl Acad Sci USA 1998; 95: 548–53.

    Article  PubMed  CAS  Google Scholar 

  51. Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature 1995; 378: 386–90.

    Article  PubMed  CAS  Google Scholar 

  52. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ. Defective hematopoiesis and vasculogenesis in transforming growth factor-131 knock-out mice. Development 1995; 121: 1845–54.

    PubMed  CAS  Google Scholar 

  53. Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, Lemke G. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature 1995; 378: 390–94.

    Article  PubMed  CAS  Google Scholar 

  54. Lee KF, Simon H, Chen H, Bates B, Hung MC, Hauser C. Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 1995; 378: 394–98.

    Article  PubMed  CAS  Google Scholar 

  55. Oshima M, Oshima H, Taketo MM. TGF-a receptor type II deficiency results in defective yolk sac hematopoiesis and vasculogenesis. Dev Biol 1996; 179: 297–302.

    Article  PubMed  CAS  Google Scholar 

  56. Wojnowski L, Zimmer AM, Beck TW, Hahn H, Bernal R, Rapp UR, Zimmer A. Endothelial apoptosis in Braf-deficient mice. Nat Genet 1997; 16: 293–97.

    Article  PubMed  CAS  Google Scholar 

  57. Henkemeyer M, Rossi DJ, Holmyard DP, Puri MC, Mbamalu G, Harpal K, Shih TS, Jacks T, Pawson T. Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature 1995; 377: 695–701.

    Article  PubMed  CAS  Google Scholar 

  58. Wang DZ, Hammond VE, Abud HE, Bertoncello I, McAvoy JW, Bowtell DD. Mutation in Sos 1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for Sos 1 in EGFR signaling and development. Genes Dev 1997; 11: 309–20.

    Article  PubMed  CAS  Google Scholar 

  59. Offermanns S, Mancino V, Revel JP, Simon MI. Vascular system defects and impaired cell chemokinesis as a result of G [alpha] l3 deficiency. Science 1997; 275: 533–36.

    Article  PubMed  CAS  Google Scholar 

  60. Fournier E, Dubreuil P, Birnbaum D, Borg JP. Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming capacity of the FLT4 receptor. Oncogene 1995; 11: 921–31.

    PubMed  CAS  Google Scholar 

  61. Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U, Risau W. Angiopoietin-1 induces sprouting angiogenesis in vitro. Curr Biol 1998; 23: 529–32.

    Article  Google Scholar 

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Authors
  1. Thomas I. Koblizek
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  2. Werner Risau
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  3. Urban Deutsch
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Editor information

Editors and Affiliations

  1. Department of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands

    Pieter A. Doevendans

  2. Academic Hospital Maastricht, CARIM, Maastricht, The Netherlands

    Robert S. Reneman

  3. Department of Physiology, Academic Hospital Maastricht, Maastricht, The Netherlands

    Marc van Bilsen

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Koblizek, T.I., Risau, W., Deutsch, U. (1999). Receptor Tyrosine Kinase Signaling in Vasculogenesis and Angiogenesis. In: Doevendans, P.A., Reneman, R.S., van Bilsen, M. (eds) Cardiovascular Specific Gene Expression. Developments in Cardiovascular Medicine, vol 214. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9321-2_17

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  • DOI: https://doi.org/10.1007/978-94-015-9321-2_17

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5189-9

  • Online ISBN: 978-94-015-9321-2

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