The vascular system is a complex network of vessels that carries oxygenated blood and nutrients throughout our bodies. It comes as no surprise that angiogenesis, the process of growing new blood vessels, occurs not only in health, but also in serious disease, where it may be either up- or down-regulated. While the growth of the vascular system is one of the earlier events of embryogenesis, angiogenesis also occurs in adulthood, during wound healing and restoration of blood flow to injured tissues. The healthy body controls angiogenesis through a perfect balance of modulators, regulated by a strong interaction between growth factors and inhibitors, the imbalance of which can lead to disease. Angiogenesis is a “common denominator” shared by diseases affecting more than one billion people worldwide; these diseases are caused by both excessive angiogenesis (cancer, diabetic eye disease, rheumatoid arthritis), and insufficient angiogenesis (coronary heart disease, stroke, delayed wound healing) [1].


Vascular Endothelial Growth Factor Endothelial Progenitor Cell Vascular Endothelial Growth Factor Production Intussusceptive Angiogenesis Excessive Angiogenesis 
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  1. 1.
    DeWitt N (2005) Angiogenesis. Nature 438(7070):931CrossRefGoogle Scholar
  2. 2.
    Flamme I, Frolich T, Risau W (1997) Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol 173:206–210CrossRefPubMedGoogle Scholar
  3. 3.
    Asahara T, Isner JM (2002) Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res 2:171–178CrossRefGoogle Scholar
  4. 4.
    Isner JM, Asahara T (1999) Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 103:1231–1236CrossRefPubMedGoogle Scholar
  5. 5.
    Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395CrossRefPubMedGoogle Scholar
  6. 6.
    Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31CrossRefPubMedGoogle Scholar
  7. 7.
    Serini G, Ambrosi D, Giraudo E et al (2003) Modeling the early stages of vascular network assembly. EMBO J 22:1771–1779CrossRefPubMedGoogle Scholar
  8. 8.
    Hacohen N, Kramer S, Sutherland D et al (1998) Sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell 92:253–263CrossRefPubMedGoogle Scholar
  9. 9.
    Gerhardt H, Golding M, Fruttiger M et al (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163–1177CrossRefPubMedGoogle Scholar
  10. 10.
    Djonov V, Schmid M, Tschanz SA, Burri PH (2000) Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circ Res 86:286–292PubMedGoogle Scholar
  11. 11.
    Folkman J, D’Amore PA (1996) Blood vessel formation: what is its molecular basis? Cell 87:1153–1155CrossRefPubMedGoogle Scholar
  12. 12.
    Hellstrom M, Kalen M, Lindahl P et al (1999) Role of PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055PubMedGoogle Scholar
  13. 13.
    Gale NW, Baluk P, Pan L et al (2001) Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Dev Biol 230:151–160CrossRefPubMedGoogle Scholar
  14. 14.
    Augustin HG (2001) Tubes, branches, and pillars: the many ways of forming a new vasculature. Circ Res 89:645–647PubMedGoogle Scholar
  15. 15.
    Rucker HK, Wynder HJ, Thomas WE (2000) Cellular mechanisms of CNS pericytes. Brain Res Bull 15 51(5):363–369CrossRefGoogle Scholar
  16. 16.
    Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21:1104–1117CrossRefPubMedGoogle Scholar
  17. 17.
    Holash J, Maisonpierre PC, Compton D et al (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994–1998CrossRefPubMedGoogle Scholar
  18. 18.
    Eriksson K, Magnusson P, Dixelius J et al (2003) Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways. FEBS Lett 536:19–24CrossRefPubMedGoogle Scholar
  19. 19.
    Gerhardt H, Golding M, Fruttiger M et al (2003) VEGF guides angiogenic sprouting utilizing endothelial tipcell filopodia. J Cell Biol 161:1163–1177CrossRefPubMedGoogle Scholar
  20. 20.
    Gunsilius E, Duba HC, Petzer AL et al (2000) Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet 355:1688–1691CrossRefPubMedGoogle Scholar
  21. 21.
    Anghelina M, Schmeisser A, Krishnan P et al (2002) Migration of monocytes/macrophages in vitro and in vivo is accompanied by MMP12-dependent tunnels formation and by neo-vascularization. Cold Spring Harb Symp Quant Biol LXVII:209–215CrossRefGoogle Scholar
  22. 22.
    Hogg N, Henderson R, Leitinger B et al (2002) Mechanisms contributing to the activity of integrins on leukocytes. Immunol Rev 186:164–171CrossRefPubMedGoogle Scholar
  23. 23.
    Moldovan NI (2002) Role of monocytes and macrophages in adult angiogenesis: a light at the tunnel’s end. J Hematother Stem Cell Res 11(2):179–194CrossRefPubMedGoogle Scholar
  24. 24.
    O’Reilly MS, Holmgren L, Shing Y et al (1994) Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328CrossRefPubMedGoogle Scholar
  25. 25.
    O’Reilly MS, Boehm T, Shing Y et al (1997) Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285CrossRefPubMedGoogle Scholar
  26. 26.
    Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039PubMedGoogle Scholar
  27. 27.
    Iruela-Arispe ML, Dvorak HF (1997) Angiogenesis: a dynamic balance of stimulators and inhibitors. Thromb Haemost 78:672–677PubMedGoogle Scholar
  28. 28.
    Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693CrossRefPubMedGoogle Scholar
  29. 29.
    Hashimoto T, Wen G, Lawton MT et al (2003) Abnormal expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in brain arteriovenus malformations. Stroke 34:925–931CrossRefPubMedGoogle Scholar
  30. 30.
    Lee CZ, Xu B, Hashimoto T et al (2004) Doxicycline suppress cerebral matrix metalloproteinase-9 and angiogenesis induced by focal hyperstimulation of vascular endothelial growth factor in a mouse model. Stroke 35:1715–1719CrossRefPubMedGoogle Scholar
  31. 31.
    Marler JJ, Fishman SJ, Kilroy SM et al (2005) Increased expression of urinary matrix metalloproteinases parallels the extent of activity of vascular anomalies. Pediatrics 116:38–45CrossRefPubMedGoogle Scholar
  32. 32.
    Folkman J, Merler E, Abernathy C, Williams G (1978) Isolation of a tumor factor responsible or angiogenesis. J Exp Med 133:275–288CrossRefGoogle Scholar
  33. 33.
    Kerbel RS (1997) A cancer therapy resistant to resistance [news; comment] [see comments] Nature 390:335–336CrossRefPubMedGoogle Scholar
  34. 34.
    Boehm T, Folkman J, Browder T, O’Reilly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance [see comments]. Nature 390:404–407CrossRefPubMedGoogle Scholar
  35. 35.
    Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4(6):423–436CrossRefPubMedGoogle Scholar
  36. 36.
    Klement G, Baruchel S, Rak J et al (2000) Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105:R15–R24CrossRefPubMedGoogle Scholar

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© Springer-Verlag Italia 2009

Authors and Affiliations

  • Alice Agliano
    • 1
  1. 1.Hematology-Oncology LaboratoryEuropean Institute of OncologyMilanItaly

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