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Physiology of Angiogenesis

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Abstract

Angiogenesis is a key prerequisite for growth in all vertebrate embryos and in many tumors. Rapid growth requires efficient transport of oxygen and metabolites. Hence, for a better understanding of tissue growth, biophysical properties of vascular systems, in addition to their molecular mechanisms, need to be investigated. The purpose of this article is twofold: (1) to discuss the biophysics of growing and perfused vascular systems in general, emphasizing non-sprouting angiogenesis and remodeling of vascular plexuses; and (2) to report on cellular details of sprouting angiogenesis in the initially non-perfused embryonic brain and spinal cord. It is concluded that (1) evolutionary optimization of the circulatory system corresponds to highly conserved vascular patterns and angiogenetic mechanisms; (2) deterministic and random processes contribute to both extraembryonic and central nervous system vascularization; (3) endothelial cells interact with a variety of periendothelial cells during angiogenesis and remodeling; and that (4) mathematical models integrating molecular, morphological and biophysical expertise improve our understanding of normal and pathological angiogenesis and account for allometric relations.

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References

  1. Roux W: Ñber die Verzweigungen der Blutgefässe. Jena, Dissertation, 1878

  2. Roux W: Gesammelte Abhandlungen über Entwicklungsmechanik der Organismen. Leipzig, Engelmann, 1895

    Google Scholar 

  3. Kurz H, Sandau K, Christ B: On the bifurcation of blood vessels-Wilhelm Roux's doctoral thesis (Jena 1878)-a seminal work for biophysical modelling in developmental biology. Anat Anz 179: 33-36, 1997

    Google Scholar 

  4. Thompson DW: On Growth and Form, Cambridge University Press, 1917

  5. Owens GK: Role of mechanical strain in regulation of differentiation of vascular smooth muscle cells. Circ Res 79: 1054-1055, 1996

    Google Scholar 

  6. Tomanek RJ, Hu N, Phan B, Clark EB: Rate of coronary vascularization during embryonic chicken development is influenced by the rate of myocardial growth. Cardiovasc Res 41: 663-671, 1999

    Google Scholar 

  7. Niklason LE, Gao J, Abbott WM, Hirschi KK, Houser S, Marini R, Langer R: Functional arteries grown in vitro. Science 284: 489-493, 1999

    Google Scholar 

  8. Christ B, Schmidt C, Huang R, Wilting J, Brand-Saberi B: Segmentation of the vertebrate body. Anat Embryol 197: 1-8, 1998

    Google Scholar 

  9. Baker CV, Bronner-Fraser M: The origins of the neural crest. Part II: an evolutionary perspective. Mech Dev 69: 13-29, 1997

    Google Scholar 

  10. Baker CV, Bronner-Fraser M: The origins of the neural crest. Part I: embryonic induction. Mech Dev 69: 3-11, 1997

    Google Scholar 

  11. LaBonne C, Bronner-Fraser M: Induction and patterning of the neural crest, a stem cell-like precursor population. J Neurobiol 36: 175-189, 1998

    Google Scholar 

  12. Groves AK, Bronner-Fraser M: Neural crest diversification. Curr Top Dev Biol 43: 221-258, 1999

    Google Scholar 

  13. Huang R, Zhi Q, Wilting J, Christ B: The fate of somitocoele cells in avian embryos. Anat Embryol 190: 243-250, 1994

    Google Scholar 

  14. Wilting J, Brand-Saberi B, Huang R, Zhi Q, Köntges G, Ordahl CP, Christ B: Angiogenic potential of the avian somite. Dev Dynam 202: 165-171, 1995

    Google Scholar 

  15. Klessinger S, Christ B: Axial structures control laterality in the distribution pattern of endothelial cells. Anat Embryol 193: 319-330, 1996

    Google Scholar 

  16. Huang R, Zhi Q, Ordahl CP, Christ B: The fate of the first avian somite. Anat Embryol 195: 435-449, 1997

    Google Scholar 

  17. Christ B, Poelmann RE, Mentink MM, Gittenberger-de Groot AC: Vascular endothelial cells migrate centripetally within embryonic arteries. Anat Embryol 181: 333-339, 1990

    Google Scholar 

  18. Wilms P, Christ B, Wilting J, Wachtler: Distribution and migration of angiogenic cells from grafted avascular intraembryonic mesoderm. Anat Embryol 183: 371-377, 1991

    Google Scholar 

  19. Nehls V, Drenckhahn D: The versatility of microvascular pericytes: from mesenchyme to smooth muscle? Histochemistry 99: 1-12, 1993

    Google Scholar 

  20. Owens GK: Molecular control of vascular smooth muscle cell differentiation. Acta Physiologica Scandinavica 164: 623-635, 1998

    Google Scholar 

  21. Hungerford JE, Little CD: Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res 36: 2-27, 1999

    Google Scholar 

  22. Drake CJ, Hungerford JE, Little CD: Morphogenesis of the first blood vessels. Ann New York Acad Sci 857: 155-179, 1998

    Google Scholar 

  23. Little CD: Vascular morphogenesis: in vivo, in vitro, in mente, Boston: Birkhäuser, 1998

    Google Scholar 

  24. Risau W: Development and differentiation of endothelium. Kidney Int 54: S3-S6, 1998

    Google Scholar 

  25. Weinstein BM: What guides early embryonic blood vessel formation? Dev Dynam 215: 2-11, 1999

    Google Scholar 

  26. Wilting J, Brand S, Kurz H, Christ B: Development of the embryonic vascular system. Cell Mol Biol Res 41: 219-232, 1995

    Google Scholar 

  27. Davies PF: Overview: temporal and spatial relationships in shear stress-mediated endothelial signalling. J Vasc Res 34: 208-211, 1997

    Google Scholar 

  28. Welsh DG, Segal SS: Endothelial and smooth muscle cell conduction in arterioles controlling blood flow. Am J Physiol 274: H178-H186, 1998

    Google Scholar 

  29. Segal SS: Cell-to-cell communication coordinates blood flow control. Hypertension 23: 1113-1120, 1994

    Google Scholar 

  30. Somlyo AP, Somlyo AV: Signal transduction and regulation in smooth muscle. Nature 372: 231-236, 1994

    Google Scholar 

  31. Hirschi KK, D'Amore PA: Pericytes in the microvasculature. Cardiovasc Res 32: 687-698, 1996

    Google Scholar 

  32. Hirschi KK, D'Amore PA: Control of angiogenesis by the pericyte: molecular mechanisms and significance. EXS 79: 419-428, 1997

    Google Scholar 

  33. Auerbach R, Auerbach W, Polakowski I: Assays for angiogenesis: a review. Pharmacol Therapeut 51: 1-11, 1991

    Google Scholar 

  34. Wilting J, Christ B, Bokeloh M: A modified chorioallantoic membrane (CAM) assay for qualitative and quantitative study of growth factors. Studies on the effects of carriers, PBS, angiogenin, and bFGF. Anat Embryol 183: 259-271, 1991

    Google Scholar 

  35. Burri PH, Tarek MR: A novel mechanism of capillary growth in the rat pulmonary microcirculation. Anat Rec 228: 35-45, 1990

    Google Scholar 

  36. Patan S, Haenni B, Burri PH: Evidence for intussusceptive capillary growth in the chicken chorio-allantoic membrane (CAM). Anat Embryol 187: 121-130, 1993

    Google Scholar 

  37. Patan S: TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res 56: 1-21, 1998

    Google Scholar 

  38. Kurz H, Ambrosy S, Wilting J, Marme D, Christ B: Proliferation pattern of capillary endothelial cells in chorioallantoic membrane development indicates local growth control, which is counteracted by vascular endothelial growth factor application. Dev Dynam 203: 174-186, 1995

    Google Scholar 

  39. Kurz H, Wilting J, Sandau K, Christ B: Automated evaluation of angiogenic effects mediated by VEGF and PlGF homo-and heterodimers. Microvasc Res 55: 92-102, 1998

    Google Scholar 

  40. Kurz H, Sandau K, Wilting J, Christ B: Blood vessel growth: mathematical analysis and computer simulation, fractality and optimality. In: Little CD, Mironov V, Sage EH (eds) Vascular Morphogenesis: in vivo, in vitro, in mente. Birkhäuser, Boston, 1998, pp 189-203

    Google Scholar 

  41. Patan S, Alvarez MJ, Schittny JC, Burri PH: Intussusceptive microvascular growth: a common alternative to capillary sprouting. Arch Histol Cytol 55 (Suppl:) 65-75, 1992

    Google Scholar 

  42. Patan S, Munn LL, Jain RK: Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res 51: 260-272, 1996

    Google Scholar 

  43. Kurz H, Christ B: Vascular development of brain and spinal cord. In: Tomanek R (ed) Assembly of the Vasculature and its Regulation. Springer, New York, 2001 (in press)

    Google Scholar 

  44. Thoma R: Ñber den Verzweigungsmodus der Arterien. Arch Entwicklungsmech 12: 352-413, 1901

    Google Scholar 

  45. Hess WR: Das Prinzip des kleinsten Kraftverbrauchs im Dienste hämodynamischer Forschung. Leipzig, Veit & Co, 1913

    Google Scholar 

  46. Suwa N, Takahashi T, Fukasawa H, Sasaki Y: Estimation of intravascular blood pressure gradient by mathematical analysis of arterial casts. Tohoku J Exp Med 79: 168-198, 1963

    Google Scholar 

  47. Mandelbrot BB: The Fractal Geometry of Nature. New York, Freeman, 1982

    Google Scholar 

  48. Spatz HC: Circulation, metabolic rate, and body size in mammals. J Comp Physiol B 161: 231-236, 1991

    Google Scholar 

  49. Murray CD: The physiological principle of minimum work: I. The vascular system and the cost of blood volume. Proc Natl Acad Sci USA 12: 207-304, 1926

    Google Scholar 

  50. Weibel ER: Fractal geometry: a design principle for living organisms. Amer J Physiol 261: L361-L369, 1991

    Google Scholar 

  51. Pries AR, Secomb TW, Gaehtgens P: Design principles of vascular beds. Circ Res 77: 1017-1023, 1995

    Google Scholar 

  52. LaBarbera M: Principles of design of fluid transport systems in zoology. Science 249: 992-1000, 1990

    Google Scholar 

  53. Kurz H: Ñber die Verzweigungen der Blutgefäße-Embryonale Musterbildung zwischen Ordnung, Zufall und Chaos. Habilitationsschrift, Universität Freiburg, 1997

  54. Kurz H, Sandau K: Modelling of blood vessel development bifurcation pattern and hemodynamics, optimality and allometry. Comments Theor Biol 4/4: 261-291, 1997

    Google Scholar 

  55. Pries AR, Secomb TW, Gaehtgens P: Structural adaptation and stability of microvascular networks: theory and simulations. Amer J Physiol 275: H349-H360, 1998

    Google Scholar 

  56. Clark EB, Hu N: Hemodynamics of the developing cardiovascular system. Ann New York Acad Sci 588: 41-47, 1990

    Google Scholar 

  57. Van Mierop LH, Bertuch CJ, Jr.: Development of arterial blood pressure in the chick embryo. Amer J Physiol 212: 43-48, 1967

    Google Scholar 

  58. Schmidt-Nielsen K: Scaling:Whyis Animal Size so Important? Cambridge, Cambridge University Press, 1989

    Google Scholar 

  59. Bennett SH, Goetzman BW, Milstein JM, Pannu JS: Role of arterial design on pulse wave reflection in a fractal pulmonary network. J Appl Physiol 80: 1033-1056, 1996

    Google Scholar 

  60. Niklason LE, Langer RS: Advances in tissue engineering of blood vessels and other tissues. Trans Immunol 5: 303-306, 1997

    Google Scholar 

  61. Sandau K, Kurz H: Modelling of vascular growth processes: a stochastic biophysical approach to embryonic angiogenesis. J Microsc 175: 205-213, 1994

    Google Scholar 

  62. Barnsley MF: Fractals Everywhere. Boston, Academic Press, 1993

    Google Scholar 

  63. Kirchner LM, Schmidt SP, Gruber BS: Quantitation of angiogenesis in the chick chorioallantoic membrane model using fractal analysis. Microvasc Res 51: 2-14, 1996

    Google Scholar 

  64. Sernetz M, Gelleri B, Hofmann J: The organism as bioreactor. Interpretation of the reduction law of metabolism in terms of heterogeneous catalysis and fractal structure. J Theor Biol 117: 209-230, 1985

    Google Scholar 

  65. West GB, Brown JH, Enquist BJ: A general model for the origin of allometric scaling laws in biology. Science 276: 122-126, 1997

    Google Scholar 

  66. West GB, Brown JH, Enquist BJ: The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science 284: 1677-1679, 1999

    Google Scholar 

  67. Kurz H, Sandau K: Allometric scaling in biology. Science 281: 751A, 1998

    Google Scholar 

  68. Sandau K, Kurz H: Measuring fractal dimension and complexity-an alternative approach with an application. J Microsc 186: 164-176, 1997

    Google Scholar 

  69. Schlatter P, König MF, Karlsson LM, Burri PH: Quantitative study of intussusceptive capillary growth in the chorioallantoic membrane (CAM) of the chicken embryo. Microvasc Res 54: 65-73, 1997

    Google Scholar 

  70. Glenny RW, Robertson HT, Yamashiro S, Bassingthwaighte JB: Applications of fractal analysis to physiology. J Appl Physiol 70: 2351-2367, 1991

    Google Scholar 

  71. Strong LH: The first appearance of vessels within the spinal cord of the mammal: Their developing patterns as far as partial formation of the dorsal septum. Acta Anat 44: 80-108, 1961

    Google Scholar 

  72. Aitkenhead M, Christ B, Eichmann A, Feucht M, Wilson DJ, Wilting J: Paracrine and autocrine regulation of vascular endothelial growth factor during tissue differentiation in the quail. Dev Dynam 212: 1-13, 1998

    Google Scholar 

  73. Breier G, Albrecht U, Sterrer S, Risau W: Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114: 521-532, 1992

    Google Scholar 

  74. Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U, Risau W: Angiopoietin-1 induces sprouting angiogenesis in vitro. Curr Biol 8: 529-532, 1998

    Google Scholar 

  75. 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 87: 1171-1180, 1996

    Google Scholar 

  76. Suri C, McClain J, Thurston G, McDonald DM, Zhou H, Oldmixon EH, Sato TN, Yancopoulos GD: Increased vascularization in mice over-expressing angiopoietin-1. Science 282: 468-471, 1998

    Google Scholar 

  77. Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R: Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumor xenografts. Science 401: 670-677, 1999

    Google Scholar 

  78. Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R: Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 13: 295-306, 1999

    Google Scholar 

  79. Kurz H, Gärtner T, Eggli PS, Christ B: First blood vessels in the avian neural tube are formed by a combination of dorsal angioblast immigration and ventral sprouting of endothelial cells. Dev Biol 173: 133-147, 1996

    Google Scholar 

  80. Cossmann PH, Eggli PS, Christ B, Kurz H: Mesoderm-derived cells proliferate in the embryonic central nervous system: confocal microscopy and three-dimensional visualization. Histochem Cell Biol 107: 205-213, 1997

    Google Scholar 

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

    Google Scholar 

  82. Plate KH: Mechanisms of angiogenesis in the brain. J Neuropathol Exp Neurol 58: 313-320, 1999

    Google Scholar 

  83. Britsch S, Christ B, Jacob HJ: The influence of cell-matrix interactions on the development of quail chorioallantoic vascular system. Anat Embryol 180: 479-484, 1989

    Google Scholar 

  84. Poelmann RE, Gittenberger-de Groot AC, Mentink MM, Delpech B, Girard N, Christ B: The extracellular matrix during neural crest formation and migration in rat embryos. Anat Embryol 182: 29-39, 1990

    Google Scholar 

  85. Strong LH: The early embryonic pattern of internal vascularization of the mammalian cerebral cortex. J Comp Neurol 123: 121-138, 1964

    Google Scholar 

  86. Halata Z, Grim M, Christ B: Origin of spinal cord meninges, sheaths of peripheral nerves, and cutaneous receptors including Merkel cells. An experimental and ultrastructural study with avian chimeras. Anat Embryol 182: 529-537, 1990

    Google Scholar 

  87. Couly GF, Le Douarin NM: Mapping of the early neural primordium in quail-chick chimeras. II. The prosencephalic neural plate and neural folds: implications for the genesis of cephalic human congenital abnormalities. Dev Biol 120: 198-214, 1987

    Google Scholar 

  88. Jaworski DM, Kelly GM, Hockfield S: The CNS-specific hyaluronan-binding protein BEHAB is expressed in ventricular zones coincident with gliogenesis. J Neurosci 15: 1352-1362, 1995

    Google Scholar 

  89. Margolis RK, Rauch U, Maurel P, Margolis RU: Neurocan and phosphacan: two major nervous tissue-specific chondroitin sulfate proteoglycans. Persp Dev Neurobiol 3: 273-290, 1996

    Google Scholar 

  90. Turley EA, Hossain MZ, Sorokan T, Jordan LM, Nagy JI: Astrocyte and microglial motility in vitro is functionally dependent on the hyaluronan receptor RHAMM. GLIA 12: 68-80, 1994

    Google Scholar 

  91. Gary SC, Kelly GM, Hockfield S: BEHAB/brevican: A brain-specific lectican implicated in gliomas and glial cell motility. Curr Opin Neurobiol 8: 576-581, 1998

    Google Scholar 

  92. Seiffert D, Iruela-Arispe ML, Sage EH, Loskutoff DJ: Distribution of vitronectin mRNA during murine development. Dev Dynam 203: 71-79, 1995

    Google Scholar 

  93. Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PMA, Sutherland G, Edwards DR: Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Brit J Cancer 79: 1828-1835, 1999

    Google Scholar 

  94. Chen WT: Proteases associated with invadopodia, and their role in degradation of extracellular matrix. Enzyme Protein 49: 59-71, 1996

    Google Scholar 

  95. Kelly T, Yan Y, Osborne RL, Athota AB, Rozypal TL, Colclasure JC, Chu WS: Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases. Clin Exp Metastasis 16: 501-512, 1998

    Google Scholar 

  96. Lamoreaux WJ, Fitzgerald ME, Reiner A, Hasty KA, Charles ST: Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvasc Res 55: 29-42, 1998

    Google Scholar 

  97. Zucker S, Mirza H, Conner CE, Lorenz AF, Drews MH, Bahou WF, Jesty J: Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer 75: 780-786, 1998

    Google Scholar 

  98. Nguyen M, Arkell J, Jackson CJ: Thrombin rapidly and efficiently activates gelatinase A in human microvascular endothelial cells via a mechanism independent of active MT1 matrix metalloproteinase. Lab Invest 79: 467-475, 1999

    Google Scholar 

  99. Nehls V, Herrmann R, Huhnken M: Guided migration as a novel mechanism of capillary network remodeling is regulated by basic fibroblast growth factor. Histochem Cell Biol 109: 319-329, 1998

    Google Scholar 

  100. Bär T, Guldner FH, Wolff JR: 'Seamless' endothelial cells of blood capillaries. Cell Tiss Res 235: 99-106, 1984

    Google Scholar 

  101. Bär T, Wolff JR: The formation of capillary basement membranes during internal vascularization of the rat's cerebral cortex. Zeitschr Zellforsch 133: 231-248, 1972

    Google Scholar 

  102. Bär T: The vascular system of the cerebral cortex. Adv Anat Embryol and Cell Biol 59: 1-62, 1980

    Google Scholar 

  103. Caprioli A, Jaffredo T, Gautier R, Dubourg C, Dieterlen-Lievre F: Blood-borne seeding by hematopoietic and endothelial precursors from the allantois. Proc Natl Acad Sci USA 95: 1641-1646, 1998

    Google Scholar 

  104. Hatzopoulos AK, Folkman J, Vasile E, Eiselen GK, Rosenberg RD: Isolation and characterization of endothelial progenitor cells from mouse embryos. Development 125: 1457-1468, 1998

    Google Scholar 

  105. Korn J, Huang R, Wilting J, Christ B, Kurz H: Blood-borne endothelial precursors in embryonic CNS angiogenesis? Ann Anat 181: 276, 1999

    Google Scholar 

  106. Kurz H, Korn J, Wilting J, Christ B: Blood-borne angioblasts in avian embryos? Keystone Symp Angiogen Vasc Remodeling X8: 126, 1998

    Google Scholar 

  107. Kurz H, Christ B: Embryonic CNS macrophages and microglia do not stem from circulating, but from extravascular precursors. GLIA 22: 98-102, 1998

    Google Scholar 

  108. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM: Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964-967, 1997

    Google Scholar 

  109. Goldbrunner RH, Bernstein JJ, Plate KH, Vince GH, Roosen K, Tonn JC: Vascularization of human glioma spheroids implanted into rat cortex is conferred by two distinct mechanisms. J Neurosci Res 55: 486-495, 1999

    Google Scholar 

  110. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM: VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18: 3964-3972, 1999

    Google Scholar 

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

    Google Scholar 

  112. Cuadros MA, Navascues J: The origin and differentiation of microglial cells during development. Prog Neurobiol 56: 173-189, 1998

    Google Scholar 

  113. Suzuki T, Ogata A, Tashiro K, Nagashima K, Tamura M, Nishihira J: Augmented expression of macrophage inhibitory factor MIF in the telencephalon of the developing rat brain. Brain Res 816: 457-462, 1999

    Google Scholar 

  114. Earle KL, Mitrofanis J: Development of glia and blood vessels in the internal capsule of rats. J Neurocytol 27: 127-139, 1998

    Google Scholar 

  115. Pennell NA, Streit WJ: Colonization of neural allografts by host microglial cells: relationship to graft neovascularization. Cell Transplant 6: 221-230, 1997

    Google Scholar 

  116. Roncali L, Virgintino D, Coltey P, Bertossi M, Errede M, Ribatti D, Nico B, Mancini L, Sorino S, Riva A: Morphological aspects of the vascularization in intraventricular neural transplants from embryo to embryo. Anat Embryol 193: 191-203, 1996

    Google Scholar 

  117. Andjelkovic AV, Nikolic B, Pachter JS, Zecevic N: Macrophages/microglial cells in human central nervous system during development: an immunohistochemical study. Brain Res 814: 13-25, 1998

    Google Scholar 

  118. Streit WJ, Graeber MB: Heterogeneity of microglial and perivascular cell populations: insights gained from the facial nucleus paradigm. GLIA 7: 68-74, 1993

    Google Scholar 

  119. Angelov DN, Neiss WF, Streppel M, Walther M, Guntinas-Lichius O, Stennert E: ED2-positive perivascular cells act as neuronophages during delayed neuronal loss in the facial nucleus of the rat. GLIA 16: 129-139, 1996

    Google Scholar 

  120. Angelov DN, Walther M, Streppel M, Guntinas-Lichius O, Neiss WF: The cerebral perivascular cells. Adv Anat Embryol Cell Biol 147: 1-87, 1998

    Google Scholar 

  121. Hurley SD, Walter SA, Semple-Rowland SL, Streit WJ: Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid microglia of the developing rat central nervous system. GLIA 25: 304-309, 1999

    Google Scholar 

  122. Lehrmann E, Kiefer R, Christensen T, Toyka KV, Zimmer J, Diemer NH, Hartung HP, Finsen B: Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats. GLIA 24: 437-448, 1998

    Google Scholar 

  123. Moore S, Thanos S: The concept of microglia in relation to central nervous system disease and regeneration. Prog Neurobiol 48: 441-460, 1996

    Google Scholar 

  124. Morioka T, Kalehua AN, Streit WJ: Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. J Comp Neurol 327: 123-132, 1993

    Google Scholar 

  125. Streit WJ: Microglial-neuronal interactions. J Chem Neuroanat 6: 261-266, 1993

    Google Scholar 

  126. Streit WJ: The role of microglia in brain injury. Neurotoxicology 17: 671-678, 1996

    Google Scholar 

  127. Draeger A, England C: The intima: historic literature revisited. Anat Anz 180: 189-192, 1998

    Google Scholar 

  128. Kohler A, Jostarndt-Fögen K, Alliegro MC, Rottner C, Draeger A: Intima-like smooth muscle cells: developmental link between endothelium and media? Anat Embryol 200: 313-323, 1999

    Google Scholar 

  129. Herman IM, D'Amore PA: Microvascular pericytes contain muscle and nonmuscle actins. J Cell Biol 101: 43-52, 1985

    Google Scholar 

  130. Nehls V, Drenckhahn D: Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113: 147-154, 1991

    Google Scholar 

  131. Yablonka-Reuveni Z, Schwartz SM, Christ B: Development of chicken aortic smooth muscle: expression of cytoskeletal and basement membrane proteins defines two distinct cell phenotypes emerging from a common lineage. Cell Mol Biol Res 41: 241-249, 1995

    Google Scholar 

  132. Yablonka-Reuveni Z, Christ B, Benson JM: Transitions in cell organization and in expression of contractile and extracellular matrix proteins during development of chicken aortic smooth muscle: evidence for a complex spatial and temporal differentiation program. Anat Embryol 197: 421-437, 1998

    Google Scholar 

  133. Bergwerff M, Verberne ME, DeRuiter MC, Poelmann RE, Gittenberger-de Groot AC: Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82: 221-231, 1998

    Google Scholar 

  134. Ehler E, Karlhuber G, Bauer HC, Draeger A: Heterogeneity of smooth muscle-associated proteins in mammalian brain microvasculature. Cell Tiss Res 279: 393-403, 1995

    Google Scholar 

  135. Bertossi M, Riva A, Congiu T, Virgintino D, Nico B, Roncali L: A compared TEM/SEM investigation on the pericytic investment in developing microvasculature of the chick optic tectum. J Submicrosc Cytol Pathol 27: 349-358, 1995

    Google Scholar 

  136. Bär T, Budi SA: Identification of pericytes in the central nervous system by silver staining of the basal lamina. Cell Tiss Res 236: 491-493, 1984

    Google Scholar 

  137. D'Amore PA, Smith SR: Growth factor effects on cells of the vascular wall: a survey. Growth Factors 8: 61-75, 1993

    Google Scholar 

  138. Pepper MS: Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytok Growth Fact Rev 8: 21-43, 1997

    Google Scholar 

  139. Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, Yancopoulos GD, Isner JM: Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res 83: 233-240, 1998

    Google Scholar 

  140. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Tyalor DG, Boak BB, Wendel DP: Defective angiogenesis in mice lacking endoglin. Science 284: 1534-1537, 1999

    Google Scholar 

  141. Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, Letarte M: Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 267: 19027-19030, 1992

    Google Scholar 

  142. Gougos A, Letarte M: Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265: 8361-8364, 1990

    Google Scholar 

  143. Lastres P, Letamendia A, Zhang H, Rius C, Almendro N, Raab U, Lopez LA, Langa C, Fabra A, Letarte M, Bernabeu C: Endoglin modulates cellular responses to TGF-beta 1. J Cell Biol 133: 1109-1121, 1996

    Google Scholar 

  144. Rius C, Smith JD, Almendro N, Langa C, Botella LM, Marchuk DA, Vary CP, Bernabeu C: Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1. Blood 92: 4677-4690, 1998

    Google Scholar 

  145. Adam PJ, Clesham GJ, Weissberg PL: Expression of endoglin mRNA and protein in human vascular smooth muscle cells. Biochem Biophys Res Comm 247: 33-37, 1998

    Google Scholar 

  146. Lindahl P, Johansson BR, Leveen P, Betsholtz C: Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277: 242-245, 1997

    Google Scholar 

  147. Lindahl P, Hellstrom M, Kalen M, Betsholtz C: Endothelial-perivascular cell signaling in vascular development: lessons from knockout mice. Curr Opin Lipidol 9: 407-411, 1998

    Google Scholar 

  148. Oh SJ, Kurz H, Christ B, Wilting J: Platelet-derived growth factor-B induces transformation of fibrocytes into spindle-shaped myofibroblasts in vivo. Histochem Cell Biol 109: 349-357, 1998

    Google Scholar 

  149. Hirschi KK, Rohovsky SA, Beck LH, Smith SR, D'Amore PA: Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res 84: 298-305, 1999

    Google Scholar 

  150. Benjamin LE, Hemo I, Keshet E: A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125: 1591-1598, 1998

    Google Scholar 

  151. Balabanov R, Beaumont T, Dore-Duffy P: Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes. J Neurosci Res 55: 578-587, 1999

    Google Scholar 

  152. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E: Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 103: 159-165, 1999

    Google Scholar 

  153. 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 277: 55-60, 1997

    Google Scholar 

  154. H, Zechner U, Orth A, Fundele R: Lack of correlation between placenta and offspring size in mouse interspecific crosses. Anat Embryol 200: 335-343, 1999

    Google Scholar 

  155. Coffey DS: Self-organization, complexity and chaos: the new biology for medicine. Nature Medicine 4: 882-885, 1998

    Google Scholar 

  156. Murray JD: Use and abuse of fractal theory in neuroscience. J Comp Neurol 361: 369-370, 1995

    Google Scholar 

  157. Patan S, Haenni B, Burri PH: Implementation of intussusceptive microvascular growth in the chicken chorioallantoic membrane (CAM). Microvasc Res 53: 33-52, 1997

    Google Scholar 

  158. Wolff JR, Bär T: 'Seamless' endothelia in brain capillaries during development of the rat's cerebral cortex. Brain Res 41: 17-24, 1972

    Google Scholar 

  159. Wilting J, Birkenhager R, Eichmann A, Kurz H, Martiny-Baron G, Marme D, McCarthy JE, Christ B, Weich HA: VEGF121 induces proliferation of vascular endothelial cells and expression of flk-1 without affecting lymphatic vessels of chorioallantoic membrane. Dev Biol 176: 76-85, 1996

    Google Scholar 

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  1. Institute of Anatomy II, University of Freiburg, Freiburg, Germany

    Haymo Kurz

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Kurz, H. Physiology of Angiogenesis. J Neurooncol 50, 17–35 (2000). https://doi.org/10.1023/A:1006485716743

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