Molecular and Cellular Biochemistry

, Volume 264, Issue 1–2, pp 99–102 | Cite as

Integrative signaling in angiogenesis

  • Michael Simons
Article

Abstract

Angiogenesis is a complex process requiring integration of multiple signals in order to achieve successful development of the new vasculature. While individual activities of numerous growth factors are well understood, the integration of their signaling at the cellular and tissue level is just beginning to be appreciated. This review focuses on these two process using vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) as examples. (Mol Cell Biochem 264: 99–102, 2004)

growth factors FGF VEGF arteriogenesis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med 6: 389–395, 2000CrossRefPubMedGoogle Scholar
  2. 2.
    Helisch A, Schaper W: Arteriogenesis: The development and growth of collateral arteries. Microcirculation 10: 83–97, 2003CrossRefPubMedGoogle Scholar
  3. 3.
    Scholz D, Ziegelhoeffer T, Helisch A, Wagner S, Friedrich C, Podzuweit T, Schaper W: Contribution of arteriogenesis and angiogenesis to pos-tocclusive hindlimb perfusion in mice. J Mol Cell Cardiol 34: 775–787, 2002CrossRefPubMedGoogle Scholar
  4. 4.
    Yla-Herttuala S, Alitalo K: Gene transfer as a tool to induce therapeutic vascular growth. Nat Med 9: 694–701, 2003CrossRefPubMedGoogle Scholar
  5. 5.
    Khurana R, Simons M: Insights from angiogenesis trials using fibroblast growth factor for advanced arteriosclerotic disease. Trends Cardiovasc Med 13: 116–122, 2003CrossRefPubMedGoogle Scholar
  6. 6.
    Post MJ, Laham R, Sellke FW, Simons M: Therapeutic angiogenesis in cardiology using protein formulations. Cardiovasc Res 49: 522–531, 2001.CrossRefPubMedGoogle Scholar
  7. 7.
    Vincent KA, Feron O, Kelly RA: Harnessing the response to tissue hypoxia: HIF-1 alpha and therapeutic angiogenesis. Trends Cardiovasc Med 12: 362–367, 2002CrossRefPubMedGoogle Scholar
  8. 8.
    Schaper W, Scholz D: Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol 23: 1143–1151, 2003CrossRefPubMedGoogle Scholar
  9. 9.
    Voskuil M, van Royen N, Hoefer IE, Seidler R, Guth BD, Bode C, Schaper W, Piek JJ, Buschmann IR: Modulation of collateral artery growth in a porcine hindlimb ligation model using MCP-1. AmJ Physiol Heart Circ Physiol 284: H1422–H1428, 2003Google Scholar
  10. 10.
    van Royen N, Hoefer I, Buschmann I, Kostin S, Voskuil M, Bode C, Schaper W, Piek JJ: Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits. Cardiovasc Res 57: 178–185, 2003CrossRefPubMedGoogle Scholar
  11. 11.
    Fukumura D, Gohongi T, Kadambi A, Izumi Y, Ang J, Yun CO, Buerk DG, Huang PL, Jain RK: Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Proc Natl Acad Sci USA 98: 2604–2609, 2001CrossRefPubMedGoogle Scholar
  12. 12.
    Matsunaga T, Warltier DC, Weihrauch DW, Moniz M, Tessmer J, Chilian WM: Ischemia-induced coronary collateral growth is dependent on vascular endothelial growth factor and nitric oxide. Circulation 102: 3098–3103, 2000PubMedGoogle Scholar
  13. 13.
    Shizukuda Y, Tang S, Yokota R, Ware JA: Vascular endothelial growth factor-induced endothelial cell migration and proliferation depend on a nitric oxide-mediated decrease in protein kinase Cdelta activity. Circ Res 85: 247–256, 1999PubMedGoogle Scholar
  14. 14.
    Li J, Post M, Volk R, Gao Y, Li M, Metais C, Sato K, Tsai J, Aird W, Rosenberg RD, Hampton TG, Sellke F, Carmeliet P, Simons M: PR39, a peptide regulator of angiogenesis. Nat Med 6: 49–55, 2000CrossRefPubMedGoogle Scholar
  15. 15.
    Li J, Shworak NW, Simons M: Increased responsiveness of hypoxic endothelial cells to FGF2 is mediated by HIF-1alpha-dependent regulation of enzymes involved in synthesis of heparan sulfate FGF2-binding sites. J Cell Sci 115: 1951–1959, 2002PubMedGoogle Scholar
  16. 16.
    Deindl E, Hoefer IE, Fernandez B, Barancik M, Heil M, Strniskova M, Schaper W: Involvement of the fibroblast growth factor system in adaptive and chemokine-induced arteriogenesis. Circ Res 92: 561–568, 2003CrossRefPubMedGoogle Scholar
  17. 17.
    Seghezzi G, Patel S, Ren CJ, Gualandris A, Pintucci G, Robbins ES, Shapiro RL, Galloway AC, Rifkin DB, Mignatti P: Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contributing to angiogenesis. J Cell Biol 141: 1659–1673, 1998CrossRefPubMedGoogle Scholar
  18. 18.
    Claffey KP, Abrams K, Shih SC, Brown LF, Mullen A, Keough M: Fibroblast growth factor 2 activation of stromal cell vascular endothelial growth factor expression and angiogenesis. Lab Invest 81: 61–75, 2001PubMedGoogle Scholar
  19. 19.
    Tomanek RJ, Holifield JS, Reiter RS, Sandra A, Lin JJ: Role of VEGF family members and receptors in coronary vessel formation. Dev Dyn 225: 233–240, 2002CrossRefPubMedGoogle Scholar
  20. 20.
    Fambrough D, McClure K, Kazlauskas A, Lander ES: Diverse signaling pathways activated by growth factor receptors induce broadly overlap-ping, rather than independent, sets of genes. Cell 97: 727–741, 1999CrossRefPubMedGoogle Scholar
  21. 21.
    Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13: 9–22, 1999PubMedGoogle Scholar
  22. 22.
    Matsumoto T, Claesson-Welsh L: VEGF receptor signal transduction. Sci STKE 2001: RE21, 2001Google Scholar
  23. 23.
    Szebenyi G, Fallon JF: Fibroblast growth factors as multifunctional signaling factors. Int Rev Cytol 185: 45–106, 1999PubMedGoogle Scholar
  24. 24.
    Simons M, Horowitz A: Syndecan-4-mediated signalling. Cell Signal 13: 855–862, 2001CrossRefPubMedGoogle Scholar
  25. 25.
    Eliceiri BP, Cheresh DA: The role of alphav integrins during angiogen-esis: insights into potential mechanisms of action and clinical development. J Clin Invest 103: 1227–1230, 1999PubMedGoogle Scholar
  26. 26.
    Stupack DG, Cheresh DA: ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci STKE 2002: PE7, 2002Google Scholar
  27. 27.
    Zachary I, Gliki G: Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res 49: 568–581, 2001CrossRefPubMedGoogle Scholar
  28. 28.
    Parenti A, Morbidelli L, Cui XL, Douglas JG, Hood JD, Granger HJ, Ledda F, Ziche M: Nitric oxide is an upstream signal of vascular endothelial growth factor-induced extracellular signal-regulated kinase 1/2 activation in postcapillary endothelium. J Biol Chem 273: 4220–4226, 1998CrossRefPubMedGoogle Scholar
  29. 29.
    Eliceiri BP, Puente XS, Hood JD, Stupack DG, Schlaepfer DD, Huang XZ, Sheppard D, Cheresh DA: Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling. J Cell Biol 157: 149–160, 2002CrossRefPubMedGoogle Scholar
  30. 30.
    Pages G, Milanini J, Richard DE, Berra E, Gothie E, Vinals F, Pouyssegur J: Signaling angiogenesis via p42/p44 MAP kinase cascade. Ann NY Acad Sci 902: 187–200, 2000PubMedGoogle Scholar
  31. 31.
    Pintucci G, Moscatelli D, Saponara F, Biernacki PR, Baumann FG, Bizekis C, Galloway AC, Basilico C, Mignatti P:Lack of ERKactivation and cell migration in FGF-2-deficient endothelial cells. FASEB J 16: 598–600, 2002PubMedGoogle Scholar
  32. 32.
    Horowitz A, Tkachenko E, Simons M: Fibroblast growth factor-specific modulation of cellular response by syndecan-4. J Cell Biol 157: 715–725, 2002PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Michael Simons
    • 1
  1. 1.Angiogenesis Research Center and Section of CardiologyDartmouth Medical School, Dartmouth-Hitchcock Medical CenterLebanonUSA

Personalised recommendations