Reactive Oxygen Species in Physiologic and Pathologic Angiogenesis

  • Alisa Morss Clyne
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 12)


Reactive oxygen species (ROS), including superoxide and hydrogen peroxide, play a major role in angiogenesis. High ROS doses induce oxidative stress and subsequent cell death in a variety of cardiovascular diseases, including hypertension and atherosclerosis. However, low doses of externally applied ROS directly promote angiogenesis by causing sub-lethal cell membrane damage and subsequent fibroblast growth factor-2 release, by increasing growth factor production, or by enhancing growth factor binding to their receptors. Once angiogenic growth factor signaling is initiated, ROS are produced intracellularly through NAD(P)H oxidases and manganese superoxide dismutase as messengers in downstream growth factor signaling for proliferation, migration, and tube formation. This chapter discusses our current understanding of the vascular ROS balance in both physiologic and pathologic angiogenesis, as well as innovative approaches to applying ROS to induce angiogenesis.


Reactive Oxygen Species Vascular Endothelial Growth Factor NADPH Oxidase Vascular Endothelial Growth Factor Expression Dielectric Barrier Discharge 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Kalluri, R.: Basement membranes: structure, assembly and role in tumour angiogenesis. Nat. Rev. Cancer 3(6), 422–433 (2003)Google Scholar
  2. 2.
    Ushio-Fukai, M., Alexander, R.: Reactive oxygen species as mediators of angiogenesis signaling. Role of NAD(P)H oxidase. Mol. Cell. Biochem. 264(1), 85–97 (2005)Google Scholar
  3. 3.
    Taniyama, Y., Griendling, K.K.: Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 42(6), 1075–1081 (2003)Google Scholar
  4. 4.
    Ogita, H., Liao, J.: Endothelial function and oxidative stress. Endothelium 11(2), 123–132 (2004)Google Scholar
  5. 5.
    Adly, A.A.M.: Oxidative stress and disease: an updated review. Res. J. Immunol. 3(2), 129–145 (2010)Google Scholar
  6. 6.
    Cross, C.E., et al.: Oxygen radicals and human disease. Ann. Intern. Med. 107(4), 526–545 (1987)Google Scholar
  7. 7.
    Halliwell, B., Gutteridge, J.M.C.: Free Radicals in Biology and Medicine, 4th edn. Oxford University Press, New York (2007)Google Scholar
  8. 8.
    Droge, W.: The plasma redox state and ageing. Ageing Res. Rev. 1(2), 257–278 (2002)Google Scholar
  9. 9.
    Hensley, K., et al.: Reactive oxygen species, cell signaling, and cell injury. Free Radic. Biol. Med. 28(10), 1456–1462 (2000)Google Scholar
  10. 10.
    Klotz, L., Kroncke, K., Sies, H.: Singlet oxygen-induced signaling effects in mammalian cells. Photochem. Photobiol. Sci. 2(2), 88–94 (2003)Google Scholar
  11. 11.
    Halliwell, B.: Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am. J. Med. 91(3, Supplement 3), S14–S22 (1991)Google Scholar
  12. 12.
    Fridovich, I.: Superoxide radical—an endogenous toxicant. Annu. Rev. Pharmacol. Toxicol. 23, 239–257 (1983)Google Scholar
  13. 13.
    Herrlich, P., Böhmer, F.D.: Redox regulation of signal transduction in mammalian cells. Biochem. Pharmacol. 59(1), 35–41 (2000)Google Scholar
  14. 14.
    Chiarugi, P., Cirri, P.: Redox regulation of protein tyrosine phosphatases during receptor tyrosine kinase signal transduction. Trends Biochem. Sci. 28(9), 509–514 (2003)Google Scholar
  15. 15.
    Hampton, M.B., Morgan, P.E., Davies, M.J.: Inactivation of cellular caspases by peptide-derived tryptophan and tyrosine peroxides. FEBS Lett. 527(1), 289–292 (2002)Google Scholar
  16. 16.
    Halliwell, B., Clement, M.V., Long, L.H.: Hydrogen peroxide in the human body. FEBS Lett. 486(1), 10–13 (2000)Google Scholar
  17. 17.
    Bienert, G.P., et al.: Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J. Biol. Chem. 282(2), 1183–1192 (2007)Google Scholar
  18. 18.
    Bienert, G.P., Schjoerring, J.K., Jahn, T.P.: Membrane transport of hydrogen peroxide. Biochimica et Biophysica Acta (BBA)—Biomembranes 1758(8), 994–1003 (2006)Google Scholar
  19. 19.
    Sen, C., Packer, L.: Antioxidant and redox regulation of gene transcription. FASEB J. 10(7), 709–720 (1996)Google Scholar
  20. 20.
    Dalton, T.P., Howard, S.G., Puga, A.: Regulation of gene expression by reactive oxygen. Ann. Rev. Pharmacol. Toxicol. 39, 67–101 (1999)Google Scholar
  21. 21.
    Schreck, R., Rieber, P., Baeuerle, P.A.: Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kB transcription factor and HIV-1. The EMBO J. 10(8), 2247–2258 (1991)Google Scholar
  22. 22.
    Wang, X., et al.: The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem. J. 333(Pt 2), 291–300 (1998)Google Scholar
  23. 23.
    Griendling, K.K., Harrison, D.G.: Dual role of reactive oxygen species in vascular growth. Circ. Res. 85(6), 562–563 (1999)Google Scholar
  24. 24.
    Bielski, B.H.J., Cabelli, D.E.: ChemInform abstract: superoxide and hydroxyl radical chemistry in aqueous solution. In: Foote, C.S. (ed.) Active Oxygen in Chemistry. Chapman & Hall, Glasgow (1996)Google Scholar
  25. 25.
    Halliwell, B.: Oxygen and nitrogen are pro-carcinogens. damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat. Res./Genet. Toxicol. Environ. Mutagen. 443(1–2), 37–52 (1999)Google Scholar
  26. 26.
    Stadtman, E.R., Berlett, B.S.: Fenton chemistry. Amino acid oxidation. J. Biol. Chem. 266(26), 17201–17211 (1991)Google Scholar
  27. 27.
    Buettner, G.R.: The pecking order of free radicals and antioxidants: lipid peroxidation, α-Tocopherol, and Ascorbate. Arch. Biochem. Biophys. 300(2), 535–543 (1993)Google Scholar
  28. 28.
    Fukai, T., et al.: Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ. Res. 85(1), 23–28 (1999)Google Scholar
  29. 29.
    Shaffer, J.B., Treanor, C.P., Del Vecchio, P.J.: Expression of bovine and mouse endothelial cell antioxidant enzymes following TNF-alpha exposure. Free Radic. Biol. Med. 8(5), 497–502 (1990)Google Scholar
  30. 30.
    Crosby, A.J., Wahle, K.W., Duthie, G.G.: Modulation of glutathione peroxidase activity in human vascular endothelial cells by fatty acids and the cytokine interleukin-1 beta. Biochim. Biophys. Acta 1303(3), 187–192 (1996)Google Scholar
  31. 31.
    Li, P.F., Fang, Y.Z., Lu, X.: Oxidative modification of bovine erythrocyte superoxide dismutase by hydrogen peroxide and ascorbate—Fe(III). Biochem. Mol. Biol. Int. 29(5), 929–937 (1993)Google Scholar
  32. 32.
    Roy, S., et al.: Dermal wound healing is subject to redox control. Mol. Ther. 13, 211–220 (2006)Google Scholar
  33. 33.
    Jones, M.K., et al.: Dual actions of nitric oxide on angiogenesis: possible roles of PKC, ERK, and AP-1. Biochem. Biophys. Res. Commun. 318, 520–528 (2004)Google Scholar
  34. 34.
    Wlaschek, M., Scharffetter-Kochanek, K.: Oxidative stress in chronic venous leg ulcers. Wound Repair Regen. 13(5), 452–461 (2005)Google Scholar
  35. 35.
    Sen, C.K., Roy, S.: Redox signals in wound healing. Biochim. Biophys. Acta 1780(11), 1348–1361 (2008)Google Scholar
  36. 36.
    Martin, K.R., Barrett, J.C.: Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity. Hum. Exp. Toxicol. 21, 71–75 (2002)Google Scholar
  37. 37.
    Lambeth, J.D.: NOX enzymes and the biology of reactive oxygen. Nat. Rev. Immunol. 4(3), 181–189 (2004)Google Scholar
  38. 38.
    Lelkes, P.I., et al.: Hypoxia/reoxygenation enhances tube formation of cultured microvascular endothelial cells: the role of reactive oxygen species. In: Maragoudakis, M.E. (ed.) Angiogenesis: Models, Modulators, and Clinical Applications, NATO ASI (1998)Google Scholar
  39. 39.
    Morss, A.S., Edelman, E.R.: Glucose modulates basement membrane fibroblast growth factor-2 via alterations in endothelial cell permeability. J. Biol. Chem. 282(19), 14635–14644 (2007)Google Scholar
  40. 40.
    Qian, Y., et al.: Hydrogen peroxide formation and actin filament reorganization by Cdc42 are essential for ethanol-induced in vitro angiogenesis. J. Biol. Chem. 278(18), 16189–16197 (2003)Google Scholar
  41. 41.
    Huang, R.P., et al.: UV activates growth factor receptors via reactive oxygen intermediates. J. Cell. Biol. 133(1), 211–220 (1996)Google Scholar
  42. 42.
    Datta, R., et al.: Involvement of reactive oxygen intermediates in the induction of c-jun gene transcription by ionizing radiation. Biochemistry 31(35), 8300–8306 (1992)Google Scholar
  43. 43.
    Shimizu, S., et al.: Stimulation by hydrogen peroxide of l-arginine metabolism to l-citrulline coupled with nitric oxide synthesis in cultured endothelial cells. Res. Commun. Chem. Pathol. Pharmacol. 84(3), 315–329 (1994)Google Scholar
  44. 44.
    Burdon, R.H., Gill, V., Rice-Evans, C.: Oxidative stress and tumour cell proliferation. Free Radic. Res. Commun. 11(1–3), 65–76 (1990)Google Scholar
  45. 45.
    Vepa, S., et al.: Hydrogen peroxide stimulates tyrosine phosphorylation of focal adhesion kinase in vascular endothelial cells. Am. J. Physiol. 277(1 Pt 1), L150–L158 (1999)Google Scholar
  46. 46.
    Luczak, K., et al.: Low concentration of oxidant and nitric oxide donors stimulate proliferation of human endothelial cells in vitro. Cell. Biol. Int. 28(6), 483–486 (2004)Google Scholar
  47. 47.
    Yasuda, M., et al.: Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 in endothelial cells. Life Sci. 64(4), 249–258 (1999)Google Scholar
  48. 48.
    Shono, T., et al.: Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol. Cell. Biol. 16(8), 4231–4239 (1996)Google Scholar
  49. 49.
    Sasaki, H., et al.: Hypoxic preconditioning triggers myocardial angiogenesis: a novel approach to enhance contractile functional reserve in rat with myocardial infarction. J. Mol. Cell. Cardiol. 34(3), 335–348 (2002)Google Scholar
  50. 50.
    Monte, M., Davel, L.E., de Lustig, E.S.: Inhibition of lymphocyte-induced angiogenesis by free radical scavengers. Free Radic. Biol. Med. 17(3), 259–266 (1994)Google Scholar
  51. 51.
    Monte, M., Davel, L.E., Sacerdote de Lustig, E.: Hydrogen peroxide is involved in lymphocyte activation mechanisms to induce angiogenesis. Eur. J. Cancer 33(4), 676–682 (1997)Google Scholar
  52. 52.
    Fidelus, R.K.: The generation of oxygen radicals: a positive signal for lymphocyte activation. Cell. Immunol. 113(1), 175–182 (1988)Google Scholar
  53. 53.
    Koch, A.E., Polverini, P.J., Leibovich, S.J.: Functional heterogeneity of human rheumatoid synovial tissue macrophages. J. Rheumatol. 15(7), 1058–1063 (1988)Google Scholar
  54. 54.
    Koch, A.E., et al.: Inhibition of production of monocyte/macrophage-derived angiogenic activity by oxygen free-radical scavengers. Cell. Biol. Int. Rep. 16(5), 415–425 (1992)Google Scholar
  55. 55.
    Yasuda, M., et al.: A novel effect of polymorphonuclear leukocytes in the facilitation of angiogenesis. Life Sci. 66(21), 2113–2121 (2000)Google Scholar
  56. 56.
    Peus, D., et al.: H2O2 is required for UVB-induced EGF receptor and downstream signaling pathway activation. Free Radic. Biol. Med. 27(11–12), 1197–1202 (1999)Google Scholar
  57. 57.
    Gamou, S., Shimizu, N.: Hydrogen peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor. FEBS Lett. 357(2), 161–164 (1995)Google Scholar
  58. 58.
    Goldkorn, T., et al.: EGF-receptor phosphorylation and signaling are targeted by H2O2 redox stress. Am. J. Respir. Cell. Mol. Biol. 19(5), 786–798 (1998)Google Scholar
  59. 59.
    Chua, C.C., Hamdy, R.C., Chua, B.H.L.: Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cells. Free Radic. Biol. Med. 25(8), 891–897 (1998)Google Scholar
  60. 60.
    Li, W.G., et al.: H(2)O(2)-induced O(2) production by a non-phagocytic NAD(P)H oxidase causes oxidant injury. J. Biol. Chem. 276(31), 29251–29256 (2001)Google Scholar
  61. 61.
    Rathore, R., et al.: Hypoxia activates NADPH oxidase to increase [ROS]i and [Ca2+]i through the mitochondrial ROS-PKCepsilon signaling axis in pulmonary artery smooth muscle cells. Free Radic. Biol. Med. 45(9), 1223–1231 (2008)Google Scholar
  62. 62.
    May, J.M., Haen, C.D.: Insulin-stimulated intracellular hydrogen peroxide production in rat epididymal fat cells. J. Biol. Chem. 254, 2214–2220 (1979)Google Scholar
  63. 63.
    Irani, K., et al.: Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 275(5306), 1649–1652 (1997)Google Scholar
  64. 64.
    Yoshizumi, M., et al.: Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species. J. Biol. Chem. 275(16), 11706–11712 (2000)Google Scholar
  65. 65.
    Bohlen, P., et al.: Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc. Natl. Acad. Sci. U S A 81, 5364–5368 (1984)Google Scholar
  66. 66.
    Cross, M.J., Claesson-Welsh, L.: FGF and VEGF function in angiogenesis: signaling pathways, biological responses and therapeutic inhibition. Trends Pharmacol. Sci. 22(4), 201–207 (2001)Google Scholar
  67. 67.
    Nugent, M.A., Iozzo, R.V.: Fibroblast growth factor-2. Int. J. Biochem. Cell. Biol. 32(2), 115–120 (2000)Google Scholar
  68. 68.
    Houchen, C.W., et al.: FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury. Am. J. Physiol. Gastrointest. Liver Physiol. 276(1), G249–G258 (1999)Google Scholar
  69. 69.
    Tepper, O.M., et al.: Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of FGF-2. FASEB J. 18, 1231–1233 (2004)Google Scholar
  70. 70.
    Fuks, Z., et al.: Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Res. 54, 2582–2590 (1994)Google Scholar
  71. 71.
    Haimovitz-Friedman, A., et al.: Protein kinase C mediated basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis. Cancer Res. 54(10), 2591–2597 (1994)Google Scholar
  72. 72.
    Ku, P.T., D’Amore, P.A.: Regulation of basic fibroblast growth factor (bFGF) gene and protein expression following its release from sublethally injured endothelial cells. J. Cell. Biochem. 58(3), 328–343 (1995)Google Scholar
  73. 73.
    Finklestein, S.P., et al.: Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res. 460(2), 253–259 (1988)Google Scholar
  74. 74.
    Fischer, T.A., et al.: Regulation of bFGF expression and Ang II secretion in cardiac myocytes and microvascular endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 272(2), H958–H968 (1997)Google Scholar
  75. 75.
    Weich, H.A., et al.: Transcriptional regulation of basic fibroblast growth factor gene expression in capillary endothelial cells. J. Cell. Biochem. 47(2), 158–164 (1991)Google Scholar
  76. 76.
    Jimenez, S.K., et al.: Transcriptional regulation of FGF-2 gene expression in cardiac myocytes. Cardiovas. Res. 62(3), 548–557 (2004)Google Scholar
  77. 77.
    Seghezzi, G., et al.: 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(7), 1659–1673 (1998)Google Scholar
  78. 78.
    Black, S.M., DeVol, J.M., Wedgwood, S.: Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation. Am. J. Physiol. Cell. Physiol. 294(1), C345–C354 (2008)Google Scholar
  79. 79.
    Griendling, K.K., Sorescu, D., Ushio-Fukai, M.: NAD(P)H oxidase: role in cardiovascular biology and disease. Circ. Res. 86(5), 494–501 (2000)Google Scholar
  80. 80.
    Ushio-Fukai, M., et al.: Novel role of gp91(phox)-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ. Res. 91(12), 1160–1167 (2002)Google Scholar
  81. 81.
    Abid, M.R., et al.: Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism. FASEB J. 15(13), 2548–2550 (2001)Google Scholar
  82. 82.
    Colavitti, R., et al.: Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR. J. Biol. Chem. 277(5), 3101–3108 (2002)Google Scholar
  83. 83.
    Mata-Greenwood, E., et al.: Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-beta1 and reactive oxygen species: a requirement for NAD(P)H oxidase. Am. J. Physiol. Lung Cell. Mol. Physiol. 289(2), L288–L289 (2005)Google Scholar
  84. 84.
    Connor, K.M., et al.: Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation. J. Biol. Chem. 280(17), 16916–16924 (2005)Google Scholar
  85. 85.
    Marikovsky, M., et al.: Cu/Zn superoxide dismutase plays a role in angiogenesis. Int. J. Cancer 97(1), 34–41 (2002)Google Scholar
  86. 86.
    Schreck, R., Rieber, P., Baeuerle, P.A.: Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 10(8), 2247–2258 (1991)Google Scholar
  87. 87.
    Wang, G.L., Jiang, B.H., Semenza, G.L.: Effect of altered redox states on expression and DNA-binding activity of hypoxia-inducible factor 1. Biochem. Biophys. Res. Commun. 212(2), 550–556 (1995)Google Scholar
  88. 88.
    Kietzmann, T., Gorlach, A.: Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin. Cell. Dev. Biol. 16(4–5), 474–486 (2005)Google Scholar
  89. 89.
    Kroll, J., Waltenberger, J.: The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells. J. Biol. Chem. 272(51), 32521–32527 (1997)Google Scholar
  90. 90.
    Guo, D.Q., et al.: Tumor necrosis factor employs a protein-tyrosine phosphatase to inhibit activation of KDR and vascular endothelial cell growth factor-induced endothelial cell proliferation. J. Biol. Chem. 275(15), 11216–11221 (2000)Google Scholar
  91. 91.
    Huang, L., et al.: HCPTPA, a protein tyrosine phosphatase that regulates vascular endothelial growth factor receptor-mediated signal transduction and biological activity. J. Biol. Chem. 274(53), 38183–38188 (1999)Google Scholar
  92. 92.
    Huot, J., et al.: Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ. Res. 80(3), 383–392 (1997)Google Scholar
  93. 93.
    Ushio-Fukai, M., et al.: Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells. J. Biol. Chem. 274(32), 22699–22704 (1999)Google Scholar
  94. 94.
    Wang, Y., et al.: The role of the NADPH oxidase complex, p38 MAPK, and Akt in regulating human monocyte/macrophage survival. Am. J. Respir. Cell. Mol. Biol. 36(1), 68–77 (2007)Google Scholar
  95. 95.
    Jiang, F., Zhang, Y., Dusting, G.J.: NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol. Rev. 63(1), 218–242 (2011)Google Scholar
  96. 96.
    van Wetering, S., et al.: Reactive oxygen species mediate Rac-induced loss of cell–cell adhesion in primary human endothelial cells. J. Cell Sci. 115(9), 1837–1846 (2002)Google Scholar
  97. 97.
    Moldovan, L., et al.: The actin cytoskeleton reorganization induced by Rac1 requires the production of superoxide. Antioxid. Redox. Signal. 1(1), 29–43 (1999)MathSciNetGoogle Scholar
  98. 98.
    Armstrong, D., Sohal, R.S, Cutler, R.G.: Free Radicals in Molecular Biology, Aging, and Disease. Lippincott-Raven, Philadelphia (1984)Google Scholar
  99. 99.
    Dimmeler, S., Zeiher, A.M.: Reactive oxygen species and vascular cell apoptosis in response to angiotensin II and pro-atherosclerotic factors. Regul. Pept. 90(1–3), 19–25 (2000)Google Scholar
  100. 100.
    Marui, N., et al.: Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J. Clin. Invest. 92(4), 1866–1874 (1993)Google Scholar
  101. 101.
    Chappell, D.C., et al.: Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ. Res. 82(5), 532–539 (1998)Google Scholar
  102. 102.
    Mugge, A., et al.: Release of intact endothelium-derived relaxing factor depends on endothelial superoxide dismutase activity. Am. J. Physiol. 260(2 Pt 1), C219–C225 (1991)Google Scholar
  103. 103.
    Barger, A.C., et al.: Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N. Engl. J. Med. 310(3), 175–177 (1984)Google Scholar
  104. 104.
    O’Brien, K.D., et al.: Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 93(4), 672–682 (1996)Google Scholar
  105. 105.
    De Keulenaer, G.W., et al.: Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ. Res. 82(10), 1094–1101 (1998)Google Scholar
  106. 106.
    Ohara, Y., et al.: Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation. Arterioscler. Thromb. 14(6), 1007–1013 (1994)Google Scholar
  107. 107.
    Heinloth, A., et al.: Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endothelial cells. J. Am. Soc. Nephrol. 11(10), 1819–1825 (2000)Google Scholar
  108. 108.
    Li, W.G., et al.: Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity. Free Radic. Biol. Med. 34(7), 937–946 (2003)Google Scholar
  109. 109.
    Wolfort, R.M., Stokes, K.Y., Granger, D.N.: CD4+ T lymphocytes mediate hypercholesterolemia-induced endothelial dysfunction via a NAD(P)H oxidase-dependent mechanism. Am. J. Physiol. Heart Circ. Physiol. 294(6), H2619–H2626 (2008)Google Scholar
  110. 110.
    Moulton, K.S., et al.: Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99(13), 1726–1732 (1999)Google Scholar
  111. 111.
    Tenaglia, A.N., et al.: Neovascularization in atherectomy specimens from patients with unstable angina: implications for pathogenesis of unstable angina. Am. Heart J. 135(1), 10–14 (1998)Google Scholar
  112. 112.
    Gross, J.L., Moscatelli, D., Rifkin, D.B.: Increased capillary endothelial cell protease activity in response to angiogenic stimuli in vitro. Proc. Natl. Acad. Sci. U S A 80(9), 2623–2627 (1983)Google Scholar
  113. 113.
    Galis, Z.S., et al.: Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J. Clin. Invest. 94(6), 2493–2503 (1994)Google Scholar
  114. 114.
    Sorescu, D., et al.: Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105(12), 1429–1435 (2002)Google Scholar
  115. 115.
    Ruef, J., et al.: Induction of vascular endothelial growth factor in balloon-injured baboon arteries: a novel role for reactive oxygen species in atherosclerosis. Circ. Res. 81(1), 24–33 (1997)Google Scholar
  116. 116.
    Touyz, R.M., Briones, A.M.: Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens. Res. 34(1), 5–14 (2011)Google Scholar
  117. 117.
    Landmesser, U., et al.: Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension 40(4), 511–515 (2002)Google Scholar
  118. 118.
    Jung, O., et al.: gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 109(14), 1795–1801 (2004)Google Scholar
  119. 119.
    Matsuno, K., et al.: Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 112(17), 2677–2685 (2005)Google Scholar
  120. 120.
    Gavazzi, G., et al.: Decreased blood pressure in NOX1-deficient mice. FEBS Lett. 580(2), 497–504 (2006)Google Scholar
  121. 121.
    Hutchins, P.M., Bond, R.F., Green, H.D.: Participation of oxygen in the local control of skeletal muscle microvasculature. Circ. Res. 40(4), 85–93 (1974)Google Scholar
  122. 122.
    Noon, J.P., et al.: Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J. Clin. Invest. 99(8), 1873–1879 (1997)Google Scholar
  123. 123.
    Antonios, T.F., et al.: Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension. Heart 89(2), 175–178 (2003)Google Scholar
  124. 124.
    Mourad, J.J., et al.: Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann. Oncol. 19(5), 927–934 (2008)Google Scholar
  125. 125.
    Steeghs, N., et al.: Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clin. Cancer Res. 14(11), 3470–3476 (2008)Google Scholar
  126. 126.
    Debbabi, H., et al.: Increased skin capillary density in treated essential hypertensive patients. Am. J. Hypertens. 19(5), 477–483 (2006)Google Scholar
  127. 127.
    Brown, N.S., Bicknell, R.: Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res. 3(5), 323–327 (2001)Google Scholar
  128. 128.
    Calvisi, D.F., et al.: Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer. J. Hepatol. 41(5), 815–822 (2004)Google Scholar
  129. 129.
    Azad, N., Rojanasakul, Y., Vallyathan, V.: Inflammation and lung cancer: roles of reactive oxygen/nitrogen species. J. Toxicol. Environ. Health B Crit. Rev. 11(1), 1–15 (2008)Google Scholar
  130. 130.
    Fruehauf, J.P., Trapp, V.: Reactive oxygen species: an Achilles’ heel of melanoma? Expert Rev. Anticancer Ther. 8(11), 1751–1757 (2008)Google Scholar
  131. 131.
    Szatrowski, T.P., Nathan, C.F.: Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51(3), 794–798 (1991)Google Scholar
  132. 132.
    Kamata, T.: Roles of Nox1 and other Nox isoforms in cancer development. Cancer Sci. 100(8), 1382–1388 (2009)Google Scholar
  133. 133.
    Los, M., et al.: Switching Akt: from survival signaling to deadly response. BioEssays 31(5), 492–495 (2009)Google Scholar
  134. 134.
    Muller, J.M., Rupec, R.A., Baeuerle, P.A.: Study of gene regulation by NF-kappa B and AP-1 in response to reactive oxygen intermediates. Methods 11(3), 301–312 (1997)Google Scholar
  135. 135.
    Pennington, J.D., et al.: Redox-sensitive signaling factors as a novel molecular targets for cancer therapy. Drug Resist. Updat. 8(5), 322–330 (2005)Google Scholar
  136. 136.
    North, S., Moenner, M., Bikfalvi, A.: Recent developments in the regulation of the angiogenic switch by cellular stress factors in tumors. Cancer Lett. 218(1), 1–14 (2005)Google Scholar
  137. 137.
    Chandel, N.S., et al.: Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. U S A 95(20), 11715–11720 (1998)Google Scholar
  138. 138.
    Cai, T., et al.: N-acetylcysteine inhibits endothelial cell invasion and angiogenesis. Lab. Invest. 79(9), 1151–1159 (1999)Google Scholar
  139. 139.
    Evans, J.L., et al.: Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr. Rev. 23(5), 599–622 (2002)Google Scholar
  140. 140.
    Christ, M., et al.: Glucose increases endothelial-dependent superoxide formation in coronary arteries by NAD(P)H oxidase activation: attenuation by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin. Diabetes 51(8), 2648–2652 (2002)Google Scholar
  141. 141.
    Liu, S., et al.: Glucose down-regulation of cGMP-dependent protein kinase I expression in vascular smooth muscle cells involves NAD(P)H oxidase-derived reactive oxygen species. Free Radic. Biol. Med. 42(6), 852–863 (2007)Google Scholar
  142. 142.
    Zhang, M., et al.: Glycated proteins stimulate reactive oxygen species production in cardiac myocytes: involvement of Nox2 (gp91phox)-containing NADPH oxidase. Circulation 113(9), 1235–1243 (2006)Google Scholar
  143. 143.
    Wautier, M.P., et al.: Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am. J. Physiol. Endocrinol. Metab. 280(5), E685–E694 (2001)Google Scholar
  144. 144.
    Stokes, K.Y., et al.: NAD(P)H oxidase-derived superoxide mediates hypercholesterolemia-induced leukocyte-endothelial cell adhesion. Circ. Res. 88(5), 499–505 (2001)Google Scholar
  145. 145.
    Silver, A.E., et al.: Overweight and obese humans demonstrate increased vascular endothelial NAD(P)H oxidase-p47(phox) expression and evidence of endothelial oxidative stress. Circulation 115(5), 627–637 (2007)Google Scholar
  146. 146.
    Guzik, T.J., et al.: Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105(14), 1656–1662 (2002)Google Scholar
  147. 147.
    Tsilibary, E.C.: Microvascular basement membranes in diabetes mellitus. J. Pathol. 200(4), 537–546 (2003)Google Scholar
  148. 148.
    Martin, A., Komada, M.R., Sane, D.C.: Abnormal angiogenesis in diabetes mellitus. Med. Res. Rev. 23(2), 117–145 (2003)Google Scholar
  149. 149.
    Ellis, E.A., et al.: Increased H2O2, vascular endothelial growth factor and receptors in the retina of the BBZ/Wor diabetic rat. Free Radic. Biol. Med. 28(1), 91–101 (2000)Google Scholar
  150. 150.
    Caldwell, R.B., et al.: Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr. Drug Targets 6(4), 511–524 (2005)MathSciNetGoogle Scholar
  151. 151.
    Cao, Y., Cao, R.: Angiogenesis inhibited by drinking tea. Nature 398(6726), 381 (1999)Google Scholar
  152. 152.
    Brakenhielm, E., Cao, R., Cao, Y.: Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J. 15(10), 1798–1800 (2001)Google Scholar
  153. 153.
    Schäfer, M., Werner, S.: Oxidative stress in normal and impaired wound repair. Pharmacol. Res. 58(2), 165–171 (2008)Google Scholar
  154. 154.
    Ferrara, N., Gerber, H.-P., LeCouter, J.: The biology of VEGF and its receptors. Nat. Med. 9(6), 669–676 (2003)Google Scholar
  155. 155.
    Neufeld, G., et al.: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13(1), 9–22 (1999)MathSciNetGoogle Scholar
  156. 156.
    Bikfalvi, A., et al.: Biological roles of fibroblast growth factor-2. Endocr. Rev. 18(1), 26–45 (1997)Google Scholar
  157. 157.
    Presta, M., et al.: Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 16(2), 159–178 (2005)Google Scholar
  158. 158.
    Edelman, E.R., et al.: Controlled and modulated release of basic fibroblast growth factor. Biomaterials 12(7), 619–626 (1991)Google Scholar
  159. 159.
    Borselli, C., et al.: Induction of directional sprouting angiogenesis by matrix gradients. J. Biomed. Mater. Res., Part A 80A(2), 297–305 (2007)Google Scholar
  160. 160.
    Dor, Y., et al.: Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. EMBO J. 21(8), 1939–1947 (2002)Google Scholar
  161. 161.
    Boodhwani, M., et al.: The future of therapeutic myocardial angiogenesis. Shock 26(4), 332–341 (2006)Google Scholar
  162. 162.
    Robson, M.C., Mustoe, T.A., Hunt, T.K.: The future of recombinant growth factors in wound healing. Am. J. Surg. 176(2, Supplement 1), 80S–82S (1998)Google Scholar
  163. 163.
    Simons, M., et al.: Clinical trials in coronary angiogenesis: issues, problems, consensus: an expert panel summary. Circulation 102(11), e73–e86 (2000)Google Scholar
  164. 164.
    Barlow, D.E.: Endoscopic applications of electrosurgery: a review of basic principles. Gastrointest. Endosc. 28(2), 73–76 (1982)Google Scholar
  165. 165.
    Brand, C.U., et al.: Application of argon plasma coagulation in skin surgery. Dermatology 197(2), 152–157 (1998)Google Scholar
  166. 166.
    Colt, H.G., Crawford, S.W.: In vitro study of the safety limits of bronchoscopic argon plasma coagulation in the presence of airway stents. Respirology 11(5), 643–647 (2006)Google Scholar
  167. 167.
    Raiser, J., Zenker, M.: Argon plasma coagulation for open surgical and endoscopic applications: state of the art. J. Phys. D Appl. Phys. 39, 3520–3523 (2006)Google Scholar
  168. 168.
    Robotis, J., Sechopoulos, P., Rokkas, T.: Argon plasma coagulation: clinical applications in gastroenterology. Ann. Gastroenterol. 16(2), 131–137 (2003)Google Scholar
  169. 169.
    Chirokov, A., Gutsol, A., Fridman, A.: Atmospheric pressure plasma of dielectric barrier discharges. Pure Appl. Chem. 77(2), 487–495 (2005)Google Scholar
  170. 170.
    Fridman, G., et al.: Blood coagulation and living tissue sterilization by floating-electrode dielectric barrier discharge in air. Plasma Chem. Plasma Process. 26, 425–442 (2006)Google Scholar
  171. 171.
    Soloshenko, I.A., et al.: Sterilization of medical products in low-pressure glow discharges. Plasma Phys. Rep. 26(9), 792–800 (2000)Google Scholar
  172. 172.
    Kuo, S.P., et al.: Contribution of a portable air plasma torch to rapid blood coagulation as a method of preventing bleeding. New J. Phys. 11, 115016 (2009)Google Scholar
  173. 173.
    Shekhter, A.B., et al.: Beneficial effect of gaseous nitric oxide on the healing of skin wounds. Nitric Oxide Biol. Chem. 12, 210–219 (2005)Google Scholar
  174. 174.
    Sladek, R.E.J., et al.: Plasma treatment of dental cavities: a feasibility study. IEEE Trans. Plasma Sci. 32(4), 1540–1543 (2004)Google Scholar
  175. 175.
    Sensenig, R., et al.: Non-thermal plasma induces apoptosis in melanoma cells via production of intracellular reactive oxygen species. Ann. Biomed. Eng. 39(2), 674–687 (2011)Google Scholar
  176. 176.
    Yildrim, E.D., et al.: Effect of dielectric barrier discharge plasma on the attachment and proliferation of osteoblasts cultured over poly(ε-caprolactone) scaffolds. Plasma Process Polym. 5(4), 397 (2008)Google Scholar
  177. 177.
    Eliasson, B., Egli, W., Kogelschatz, U.: Modelling of dielectric barrier discharge chemistry. Pure Appl. Chem. 66(6), 1275–1286 (1994)Google Scholar
  178. 178.
    Kuchenbecker, M., et al.: Characterization of DBD plasma source for biomedical applications. J. Phys. D: Appl. Phys. 42(4) (2009)Google Scholar
  179. 179.
    Kalghatgi, S., et al.: Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann. Biomed. Eng. 38(3), 748–757 (2010)Google Scholar
  180. 180.
    Fridman, G., et al.: Floating electrode dielectric barrier discharge plasma in air promoting apoptotic behavior in melanoma skin cancer cell lines. Plasma Chem. Plasma Process. 27(2), 163–176 (2007)MathSciNetGoogle Scholar
  181. 181.
    Clyne, A.M., Zhu, H., Edelman, E.R.: Elevated fibroblast growth factor-2 increases tumor necrosis factor-alpha induced endothelial cell death in high glucose. J. Cell. Physiol. 217(1), 86–92 (2008)Google Scholar
  182. 182.
    Muthukrishnan, L., Warder, E., McNeil, P.L.: Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruptions of endothelial cells. J. Cell. Physiol. 148(1), 1–16 (1991)Google Scholar
  183. 183.
    Caplice, N.M., et al.: Growth factors released into the coronary circulation after vascular injury promote proliferation of human vascular smooth muscle cells in culture. J. Am. Coll. Cardiol. 29(7), 1536–1541 (1997)Google Scholar
  184. 184.
    Callaghan, M.J., et al.: Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release. Plast. Reconstr. Surg. 121(1), 130–141 (2008)Google Scholar
  185. 185.
    Arjunan, K.P., et al.: Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species. J. R. Soc. Interface 9(66), 147–157 (2011)Google Scholar
  186. 186.
    Arjunan, K.P., Clyne, A.M.: Hydroxyl radical and hydrogen peroxide are primarily responsible for dielectric barrier discharge plasma-induced angiogenesis. Plasma Process. Polymers 8(12), 1154–1164Google Scholar
  187. 187.
    Petry, A., Weitnauer, M., Gorlach, A.: Receptor activation of NADPH oxidases. Antioxid. Redox Signal. 13(4), 467–487 (2010)Google Scholar
  188. 188.
    Herbert, J.M., Bono, F., Savi, P.: The mitogenic effect of H2O2 for vascular smooth muscle cells is mediated by an increase of the affinity of basic fibroblast growth factor for its receptor. FEBS Lett. 395(1), 43–47 (1996)Google Scholar
  189. 189.
    Abid, M.R., et al.: NADPH oxidase activity is required for endothelial cell proliferation and migration. FEBS Lett. 486(3), 252–256 (2000)Google Scholar
  190. 190.
    Eyries, M., Collins, T., Khachigian, L.M.: Modulation of growth factor gene expression in vascular cells by oxidative stress. Endothelium 11(2), 133–139 (2004)Google Scholar
  191. 191.
    Chang, P.Y., et al.: Particle irradiation induces FGF2 expression in normal human lens cells. Radiat. Res. 154(5), 477–484 (2000)Google Scholar

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Mechanical Engineering and MechanicsDrexel UniversityPhiladelphiaUSA

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