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Revascularization of Wounds: The Oxygen-Hypoxia Paradox

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Angiogenesis

Wound angiogenesis is rapid, accessible and controllable. Sophisticated analysis in only the last 10 years has found more and more similarities to tumor angiogenesis. One of the most striking of these similarities is that lactate production is high in both tumors and wounds, and lactate accumulation is a common feature. As it is in tumors, lactate production in wounds is not a function of hypoxia, and lactate accumulation in tissue instigates angiogenesis despite the presence of oxygen. The rate of angiogenic response is proportional to local oxygen concentration. Despite appearances, this data expands our concept of angiogenesis of all sorts. Redox regulation is an important feature.

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References

  1. Burns PA, Wilson DJ. Angiogenesis mediated by metabolites is dependent on vascular endothelial growth factor (VEGF). Angiogenesis 2003; 6: 73–7.

    Article  PubMed  CAS  Google Scholar 

  2. Murray B, Wilson DJ. A study of metabolites as intermediate effectors in angiogenesis. Angiogenesis 2001; 4: 71–7.

    Article  PubMed  CAS  Google Scholar 

  3. Semenza GL. Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1. Exp Physiol 2006; 91: 803–6.

    Article  PubMed  CAS  Google Scholar 

  4. Hunt TK, Zederfeldt B, Goldstick TK. Oxygen and healing. American Journal of Surgery 1969; 118: 521–5.

    Article  PubMed  CAS  Google Scholar 

  5. Lu H, Dalgard CL, Mohyeldin A, McFate T, Tait AS, Verma A. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J Biol Chem 2005; 280: 41928–39.

    Article  PubMed  CAS  Google Scholar 

  6. Berthod F, Germain L, Tremblay N, Auger FA. Extracellular matrix deposition by fibroblasts is necessary to promote capillary-like tube formation in vitro. J Cell Physiol 2006; 207: 491–8.

    Article  PubMed  CAS  Google Scholar 

  7. Hopf HW, Gibson JJ, Angeles AP, Constant JS, Feng JJ, Rollins MD, Zamirul Hussain M, Hunt TK. Hyperoxia and angiogenesis. Wound Repair Regen 2005; 13: 558–64.

    Article  PubMed  Google Scholar 

  8. Hunt TK, Aslam RS, Beckert S, Wagner S, Ghani QP, Hussain MZ, Roy S, Sen CK. Aerobically Derived Lactate Stimulates Revascularization and Tissue Repair via Redox Mechanisms. Antioxid Redox Signal 2007.

    Google Scholar 

  9. Myllyla R, Tuderman L, Kivirikko KI. Mechanism of the prolyl hydroxylase reaction. 2. Kinetic analysis of the reaction sequence. Eur J Biochem 1977; 80: 349–57.

    Article  PubMed  CAS  Google Scholar 

  10. Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol 2004; 558: 5–30.

    Article  PubMed  CAS  Google Scholar 

  11. Jonsson K, Jensen JA, Goodson WH, 3rd, Scheuenstuhl H, West J, Hopf HW, Hunt TK. Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann Surg 1991; 214: 605–13.

    Article  PubMed  CAS  Google Scholar 

  12. Roy S, Khanna S, Nallu K, Hunt TK, Sen CK. Dermal wound healing is subject to redox control. Mol Ther 2006; 13: 211–20.

    Article  PubMed  CAS  Google Scholar 

  13. Sen CK, Khanna S, Babior BM, Hunt TK, Ellison EC, Roy S. Oxidant-induced vascular endothelial growth factor expression in human keratinocytes and cutaneous wound healing. J Biol Chem 2002; 277: 33284–90.

    Article  PubMed  CAS  Google Scholar 

  14. Constant JS, Feng JJ, Zabel DD, Yuan H, Suh DY, Scheuenstuhl H, Hunt TK, Hussain MZ. Lactate elicits vascular endothelial growth factor from macrophages: a possible alternative to hypoxia. Wound Repair Regen 2000; 8: 353–60.

    Article  PubMed  CAS  Google Scholar 

  15. Trabold O, Wagner S, Wicke C, Scheuenstuhl H, Hussain MZ, Rosen N, Seremetiev A, Becker HD, Hunt TK. Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing. Wound Repair Regen 2003; 11: 504–9.

    Article  PubMed  Google Scholar 

  16. Rhee SG, Bae YS, Lee SR, Kwon J. Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 2000; 2000: PE1.

    Article  PubMed  CAS  Google Scholar 

  17. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. Faseb J 1996; 10: 709–20.

    PubMed  CAS  Google Scholar 

  18. Stone JR, Yang S. Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal 2006; 8: 243–70.

    Article  PubMed  CAS  Google Scholar 

  19. Biswas S, Ray M, Misra S, Dutta DP, Ray S. Is absence of pyruvate dehydrogenase complex in mitochondria a possible explanation of significant aerobic glycolysis by normal human leukocytes? FEBS Lett 1998; 425: 411–4.

    Article  PubMed  CAS  Google Scholar 

  20. Warburg O. On the origin of cancer cells. Science 1956; 123: 309–14.

    Article  PubMed  CAS  Google Scholar 

  21. Gallagher SM, Castorino JJ, Wang D, Philp NJ. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res 2007; 67: 4182–9.

    Article  PubMed  CAS  Google Scholar 

  22. Hussain MZ, Ghani QP, Hunt TK. Inhibition of prolyl hydroxylase by poly(ADP-ribose) and phosphoribosyl-AMP. Possible role of ADP-ribosylation in intracellular prolyl hydroxylase regulation. J Biol Chem 1989; 264: 7850–5.

    PubMed  CAS  Google Scholar 

  23. Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery 1981; 90: 262–70.

    PubMed  CAS  Google Scholar 

  24. Rothenfluh DA, Demhartner TJ, Fraitzl CR, Cecchini MG, Ganz R, Leunig M. Potential role of pre-existing blood vessels for vascularization and mineralization of osteochondral grafts: an intravital microscopic study in mice. Acta Orthopaed Scand 2004; 75: 359–65.

    Article  Google Scholar 

  25. Karja NW, Kikuchi K, Fahrudin M, Ozawa M, Somfai T, Ohnuma K, Noguchi J, Kaneko H, Nagai T. Development to the blastocyst stage, the oxidative state, and the quality of early developmental stage of porcine embryos cultured in alteration of glucose concentrations in vitro under different oxygen tensions. Reprod Biol Endocrinol 2006; 4: 54.

    Article  PubMed  CAS  Google Scholar 

  26. Uno K, Merges CA, Grebe R, Lutty GA, Prow TW. Hyperoxia inhibits several critical aspects of vascular development. Dev Dyn 2007; 236: 981–90.

    Article  PubMed  CAS  Google Scholar 

  27. Goldstein LJ, Gallagher KA, Bauer SM, Bauer RJ, Baireddy V, Liu ZJ, Buerk DG, Thom SR, Velazquez OC. Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells 2006; 24: 2309–18.

    Article  PubMed  CAS  Google Scholar 

  28. Bauer SM, Goldstein LJ, Bauer RJ, Chen H, Putt M, Velazquez OC. The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia. J Vasc Surg 2006; 43: 134–41.

    Article  PubMed  Google Scholar 

  29. Bluff JE, Ferguson MW, O’Kane S, Ireland G. Bone marrow-derived endothelial progenitor cells do not contribute significantly to new vessels during incisional wound healing. Exp Hematol 2007; 35: 500–6.

    Article  PubMed  CAS  Google Scholar 

  30. Gallagher KA, Goldstein LJ, Thom SR, Velazquez OC. Hyperbaric oxygen and bone marrow-derived endothelial progenitor cells in diabetic wound healing. Vascular 2006; 14: 328–37.

    Article  PubMed  Google Scholar 

  31. Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG, Nedeau A, Thom SR, Velazquez OC. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest 2007; 117: 1249–59.

    Article  PubMed  CAS  Google Scholar 

  32. Liu Y, Dulchavsky DS, Gao X, Kwon D, Chopp M, Dulchavsky S, Gautam SC. Wound repair by bone marrow stromal cells through growth factor production. J Surg Res 2006; 136: 336–41.

    Article  PubMed  CAS  Google Scholar 

  33. Folkman J. Angiogenesis and proteins of the hemostatic system.[comment]. J Thromb Haemostasis 2003; 1: 1681–2.

    Article  CAS  Google Scholar 

  34. Spencer EM, Tokunaga A, Hunt TK. Insulin-like growth factor binding protein-3 is present in the alpha-granules of platelets. Endocrinology 1993; 132: 996–1001.

    Article  PubMed  CAS  Google Scholar 

  35. Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 2007; 127: 514–25.

    Article  PubMed  CAS  Google Scholar 

  36. Decoursey TE, Ligeti E. Regulation and termination of NADPH oxidase activity. Cell Mol Life Sci 2005; 62: 2173–93.

    Article  PubMed  CAS  Google Scholar 

  37. Allen DB, Maguire JJ, Mahdavian M, Wicke C, Marcocci L, Scheuenstuhl H, Chang M, Le AX, Hopf HW, Hunt TK. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg 1997; 132: 991–6.

    PubMed  CAS  Google Scholar 

  38. Ghani QP, Wagner S, Becker HD, Hunt TK, Hussain MZ. Regulatory role of lactate in wound repair. Methods Enzymol 2004; 381: 565–75.

    Article  PubMed  CAS  Google Scholar 

  39. Wagner S, Hussain MZ, Hunt TK, Bacic B, Becker HD. Stimulation of fibroblast proliferation by lactate-mediated oxidants. Wound Repair Regen 2004; 12: 368–73.

    Article  PubMed  Google Scholar 

  40. Beckert S, Farrahi F, Aslam RS, Scheuenstuhl H, Konigsrainer A, Hussain MZ, Hunt TK. Lactate stimulates endothelial cell migration. Wound Repair Regen 2006; 14: 321–4.

    Article  PubMed  Google Scholar 

  41. Patel V, Chivukula IV, Roy S, Khanna S, He G, Ojha N, Mehrotra A, Dias LM, Hunt TK, Sen CK. Oxygen: from the benefits of inducing VEGF expression to managing the risk of hyperbaric stress. Antioxid Redox Signal 2005; 7: 1377–87.

    Article  PubMed  CAS  Google Scholar 

  42. Sen CK. The general case for redox control of wound repair. Wound Repair Regen 2003; 11: 431–8.

    Article  PubMed  Google Scholar 

  43. Ushio-Fukai M. Redox signaling in angiogenesis: role of NADPH oxidase. Cardiovasc Res 2006; 71: 226–35.

    Article  PubMed  CAS  Google Scholar 

  44. Sen CK. Cellular thiols and redox-regulated signal transduction. Curr Top Cell Regul 2000; 36: 1–30.

    Article  PubMed  CAS  Google Scholar 

  45. Sen CK, Khanna S, Gordillo G, Bagchi D, Bagchi M, Roy S. Oxygen, oxidants, and antioxidants in wound healing: an emerging paradigm. Ann NY Acad Sci 2002; 957: 239–49.

    Article  PubMed  CAS  Google Scholar 

  46. Arbiser JL, Petros J, Klafter R, Govindajaran B, McLaughlin ER, Brown LF, Cohen C, Moses M, Kilroy S, Arnold RS, Lambeth JD. Reactive oxygen generated by Nox1 triggers the angiogenic switch. Proc Natl Acad Sci USA 2002; 99: 715–20.

    Article  PubMed  CAS  Google Scholar 

  47. Cho M, Hunt TK, Hussain MZ. Hydrogen peroxide stimulates macrophage vascular endothelial growth factor release. Am J Physiol Heart Circ Physiol 2001; 280: H2357–63.

    PubMed  CAS  Google Scholar 

  48. Jackson IL, Batinic-Haberle I, Sonveaux P, Dewhirst MW, Vujaskovic Z. ROS production and angiogenic regulation by macrophages in response to heat therapy. Int J Hyperthermia 2006; 22: 263–73.

    Article  PubMed  CAS  Google Scholar 

  49. Jackson SJ, Venema RC. Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. J Nutr 2006; 136: 1178–84.

    PubMed  CAS  Google Scholar 

  50. Gengrinovitch S, Berman B, David G, Witte L, Neufeld G, Ron D. Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular chaperone for VEGF165. J Biol Chem 1999; 274: 10816–22.

    Article  PubMed  CAS  Google Scholar 

  51. Sauer H, Bekhite MM, Hescheler J, Wartenberg M. Redox control of angiogenic factors and CD31-positive vessel-like structures in mouse embryonic stem cells after direct current electrical field stimulation. Exp Cell Res 2005; 304: 380–90.

    Article  PubMed  CAS  Google Scholar 

  52. Schafer G, Cramer T, Suske G, Kemmner W, Wiedenmann B, Hocker M. Oxidative stress regulates vascular endothelial growth factor-A gene transcription through Sp1- and Sp3-dependent activation of two proximal GC-rich promoter elements. J Biol Chem 2003; 278: 8190–8.

    Article  PubMed  CAS  Google Scholar 

  53. Kosmidou I, Xagorari A, Roussos C, Papapetropoulos A. Reactive oxygen species stimulate VEGF production from C(2) C(12) skeletal myotubes through a PI3K/Akt pathway. Am J Physiol Lung Cell Mol Physiol 2001; 280: L585–92.

    PubMed  CAS  Google Scholar 

  54. Feliers D, Gorin Y, Ghosh-Choudhury G, Abboud HE, Kasinath BS. Angiotensin II stimulation of VEGF mRNA translation requires production of reactive oxygen species. Am J Physiol Renal Physiol 2006; 290: F927–36.

    Article  PubMed  CAS  Google Scholar 

  55. Kim JD, Liu L, Guo W, Meydani M. Chemical structure of flavonols in relation to modulation of angiogenesis and immune-endothelial cell adhesion. J Nutr Biochem 2006; 17: 165–76.

    Article  PubMed  CAS  Google Scholar 

  56. Sreekumar PG, Kannan R, de Silva AT, Burton R, Ryan SJ, Hinton DR. Thiol regulation of vascular endothelial growth factor-A and its receptors in human retinal pigment epithelial cells. Biochem Biophys Res Commun 2006; 346: 1200–6.

    Article  PubMed  CAS  Google Scholar 

  57. Huang SS, Zheng RL. Biphasic regulation of angiogenesis by reactive oxygen species. Pharmazie 2006; 61: 223–9.

    PubMed  CAS  Google Scholar 

  58. Zhou Q, Liu LZ, Fu B, Hu X, Shi X, Fang J, Jiang BH. Reactive oxygen species regulate insulin-induced VEGF and HIF-1{alpha} expression through the activation of p70S6K1 in human prostate cancer cells. Carcinogenesis 2006.

    Google Scholar 

  59. Gao N, Ding M, Zheng JZ, Zhang Z, Leonard SS, Liu KJ, Shi X, Jiang BH. Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species. J Biol Chem 2002; 277: 31963–71.

    Article  PubMed  CAS  Google Scholar 

  60. Matsubara T, Ziff M. Increased superoxide anion release from human endothelial cells in response to cytokines. J Immunol 1986; 137: 3295–8.

    PubMed  CAS  Google Scholar 

  61. Stone JR, Collins T. The role of hydrogen peroxide in endothelial proliferative responses. Endothelium 2002; 9: 231–8.

    Article  PubMed  CAS  Google Scholar 

  62. Abid MR, Tsai JC, Spokes KC, Deshpande SS, Irani K, Aird WC. Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism. Faseb J 2001; 15: 2548–50.

    PubMed  CAS  Google Scholar 

  63. Wang Z, Castresana MR, Newman WH. Reactive oxygen and NF-kappaB in VEGF-induced migration of human vascular smooth muscle cells. Biochem Biophys Res Commun 2001; 285: 669–74.

    Article  PubMed  CAS  Google Scholar 

  64. Colavitti R, Pani G, Bedogni B, Anzevino R, Borrello S, Waltenberger J, Galeotti T. Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR. J Biol Chem 2002; 277: 3101–8.

    Article  PubMed  CAS  Google Scholar 

  65. Ushio-Fukai M, Tang Y, Fukai T, Dikalov SI, Ma Y, Fujimoto M, Quinn MT, Pagano PJ, Johnson C, Alexander RW. Novel role of gp91(phox)-containing NAD(P) H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ Res 2002; 91: 1160–7.

    Article  PubMed  CAS  Google Scholar 

  66. Bonomo SR, Davidson JD, Yu Y, Xia Y, Lin X, Mustoe TA. Hyperbaric oxygen as a signal transducer: upregulation of platelet derived growth factor-beta receptor in the presence of HBO2 and PDGF. Undersea Hyperbaric Med 1998; 25: 211–6.

    CAS  Google Scholar 

  67. Morimoto K, Janssen WJ, Fessler MB, McPhillips KA, Borges VM, Bowler RP, Xiao YQ, Kench JA, Henson PM, Vandivier RW. Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease. J Immunol 2006; 176: 7657–65.

    PubMed  CAS  Google Scholar 

  68. Vandivier RW, Henson PM, Douglas IS. Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest 2006; 129: 1673–82.

    Article  PubMed  Google Scholar 

  69. Ferreira LS, Gerecht S, Shieh HF, Watson N, Rupnick MA, Dallabrida SM, Vunjak-Novakovic G, Langer R. Vascular Progenitor Cells Isolated From Human Embryonic Stem Cells Give Rise to Endothelial and Smooth Muscle-Like Cells and Form Vascular Networks In Vivo. Circ Res 2007.

    Google Scholar 

  70. Nareika A, He L, Game BA, Slate EH, Sanders JJ, London SD, Lopes-Virella MF, Huang Y. Sodium lactate increases LPS-stimulated MMP and cytokine expression in U937 histiocytes by enhancing AP-1 and NF-kappaB transcriptional activities. Am J Physiol Endocrinol Metab 2005; 289: E534–42.

    Article  PubMed  CAS  Google Scholar 

  71. Moldovan NI. Role of monocytes and macrophages in adult angiogenesis: a light at the tunnel’s end. J Hematother Stem Cell Res 2002; 11: 179–94.

    Article  PubMed  Google Scholar 

  72. Anghelina M, Krishnan P, Moldovan L, Moldovan NI. Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns into fibrovascular bundles. Am J Pathol2006; 168: 529–41.

    Article  PubMed  CAS  Google Scholar 

  73. Tunyogi-Csapo M, Koreny T, Vermes C, Galante JO, Jacobs JJ, Glant TT. Role of fibroblasts and fibroblast-derived growth factors in periprosthetic angiogenesis. J Orthop Res 2007.

    Google Scholar 

  74. Attard JA, Raval MJ, Martin GR, Kolb J, Afrouzian M, Buie WD, Sigalet DL. The effects of systemic hypoxia on colon anastomotic healing: an animal model. Dis Colon Rectum 2005; 48: 1460–70.

    Article  PubMed  Google Scholar 

  75. Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z, Hunt TK. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg 2000; 135: 1293–7.

    Article  PubMed  CAS  Google Scholar 

  76. Sheikh AY, Rollins MD, Hopf HW, Hunt TK. Hyperoxia improves microvascular perfusion in a murine wound model. Wound Repair Regen 2005; 13: 303–8.

    Article  PubMed  Google Scholar 

  77. Faglia E, Favales F, Aldeghi A, Calia P, Quarantiello A, Barbano P, Puttini M, Palmieri B, Brambilla G, Rampoldi A, Mazzola E, Valenti L, Fattori G, Rega V, Cristalli A, Oriani G, Michael M, Morabito A. Change in major amputation rate in a center dedicated to diabetic foot care during the 1980s: prognostic determinants for major amputation. J Diabetes Complications 1998; 12: 96–102.

    Article  PubMed  CAS  Google Scholar 

  78. Ghani QP, Wagner S, Hussain MZ. Role of ADP-ribosylation in wound repair. The contributions of Thomas K. Hunt, MD. Wound Repair Regen 2003; 11: 439–44.

    Article  PubMed  Google Scholar 

  79. Formby B, Stern R. Lactate-sensitive response elements in genes involved in hyaluronan catabolism. Biochem Biophys Res Commun 2003; 305: 203–8.

    Article  PubMed  CAS  Google Scholar 

  80. Ali MA, Yasui F, Matsugo S, Konishi T. The lactate-dependent enhancement of hydroxyl radical generation by the Fenton reaction. Free Radic Res 2000; 32: 429–38.

    Article  PubMed  CAS  Google Scholar 

  81. Wagner S, Hussain MZ, Beckert S, Ghani QP, Weinreich J, Hunt TK, Becker HD, Konigsrainer A. Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin fibroblasts. Eur J Clin Invest 2007; 37: 134–9.

    Article  PubMed  CAS  Google Scholar 

  82. Koivunen P, Hirsila M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem 2007; 282: 4524–32.

    Article  PubMed  CAS  Google Scholar 

  83. Hashimoto T, Hussien R, Oommen S, Gohil K, Brooks GA. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. Faseb J 2007.

    Google Scholar 

  84. Kumar VB, Viji RI, Kiran MS, Sudhakaran PR. Endothelial cell response to lactate: implication of PAR modification of VEGF. J Cell Physiol 2007; 211: 477–85.

    Article  PubMed  CAS  Google Scholar 

  85. Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Revn Oncol-Hematol 2006; 59: 15–26.

    Article  Google Scholar 

  86. Liu Q, Berchner-Pfannschmidt U, Moller U, Brecht M, Wotzlaw C, Acker H, Jungermann K, Kietzmann T. A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression. Proc Natl Acad Sci USA 2004; 101: 4302–7.

    Article  PubMed  CAS  Google Scholar 

  87. Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem 2002; 277: 23111–5.

    Article  PubMed  CAS  Google Scholar 

  88. Pan Y, Mansfield KD, Bertozzi CC, Rudenko V, Chan DA, Giaccia AJ, Simon MC. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol 2007; 27: 912–25.

    Article  PubMed  CAS  Google Scholar 

  89. Dalgard CL, Lu H, Mohyeldin A, Verma A. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors. Biochem J 2004; 380: 419–24.

    Article  PubMed  CAS  Google Scholar 

  90. Sen CK, Khanna S, Venojarvi M, Trikha P, Ellison EC, Hunt TK, Roy S. Copper-induced vascular endothelial growth factor expression and wound healing. Am J Physiol Heart Circ Physiol 2002; 282: H1821–7.

    PubMed  CAS  Google Scholar 

  91. Feng J, Hunt TK, Ghani P, Z. HM. Macrophage-derived angiogenic activity potential can be reversibly inhibited by ADP-ribosylation. Wound Repair Regen 1997; 5: A111.

    Google Scholar 

  92. Schreiber V, Dantzer F, Ame JC, de Murcia G. Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 2006; 7: 517–28.

    Article  PubMed  CAS  Google Scholar 

  93. Kantor J, Margolis DJ. Treatment options for diabetic neuropathic foot ulcers: a cost-effectiveness analysis. Dermatol Surg 2001; 27: 347–51.

    Article  PubMed  CAS  Google Scholar 

  94. Steed DL. Clinical evaluation of recombinant human platelet-derived growth facsmalltor for the treatment of lower extremity ulcers. Plastic Reconstructive Surg 2006; 117: 143S–149S; discussion 150S–151S.

    Article  CAS  Google Scholar 

  95. Calvert JW, Cahill J, Zhang JH. Hyperbaric oxygen and cerebral physiology. Neurol Res 2007; 29: 132–41.

    Article  PubMed  CAS  Google Scholar 

  96. Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg 2005; 92: 24–32.

    Article  PubMed  CAS  Google Scholar 

  97. Fries RB, Wallace WA, Roy S, Kuppusamy P, Bergdall V, Gordillo GM, Melvin WS, Sen CK. Dermal excisional wound healing in pigs following treatment with topically applied pure oxygen. Mutat Res 2005; 579: 172–81.

    PubMed  CAS  Google Scholar 

  98. Gordillo GM, Schlanger R, Wallace WA, Bergdall V, Bartlett R, Sen CK. Protocols for topical and systemic oxygen treatments in wound healing. Methods Enzymol 2004; 381: 575–85.

    Article  PubMed  Google Scholar 

  99. Kalliainen LK, Gordillo GM, Schlanger R, Sen CK. Topical oxygen as an adjunct to wound healing: a clinical case series. Pathophysiology 2003; 9: 81–87.

    Article  PubMed  CAS  Google Scholar 

  100. Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Therapeut 2006; 28: 1779–802.

    Article  CAS  Google Scholar 

  101. Albina JE, Mastrofrancesco B, Vessella JA, Louis CA, Henry WL, Jr., Reichner JS. HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. Am J Physiol Cell Physiol 2001; 281: C1971–7.

    PubMed  CAS  Google Scholar 

  102. Newsholme EA, Crabtree B, Ardawi MS. The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep 1985; 5: 393–400.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, University of California, San Francisco, CA, USA

    Thomas K. Hunt

  2. Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    Michael Gimbel

  3. Comprehensive Wound Center, The Ohio State University Medical Center, Columbus, OH, USA

    Chandan K. Sen

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  1. Thomas K. Hunt
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  2. Michael Gimbel
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Editors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    William D. Figg

  2. Department of Surgery Harvard Medical School and Vascular Biology Program, Children's Hospital Boston, Boston, MA, USA

    Judah Folkman

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Hunt, T.K., Gimbel, M., Sen, C.K. (2008). Revascularization of Wounds: The Oxygen-Hypoxia Paradox. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_46

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