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Hypoxia-inducible Factors and the Prevention of Acute Organ Injury

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Annual Update in Intensive Care and Emergency Medicine 2011

Part of the book series: Annual Update in Intensive Care and Emergency Medicine 2011 ((AUICEM,volume 1))

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Abstract

Hypoxic preconditioning has long been considered as organ-protective, and its clinical usage has been suggested in elective procedures, such as coronary surgery and organ transplantation. Although the mechanisms have not been clearly elucidated, it has been postulated that changes in cell-membrane composition and upregulation of various cellular protective mechanisms are responsible for a better tolerance of acute injury. Remote preconditioning (i.e., hypoxic stress in one organ conferring resistance to acute hypoxia in other organs) suggests organ cross-talk, perhaps mediated by cytokines and the immune system.

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References

  1. Bernhardt WM, Eckardt KU (2008) Physiological basis for the use of erythropoietin in critically ill patients at risk for acute kidney injury. Curr Opin Crit Care 14: 621–626

    Article  PubMed  Google Scholar 

  2. Semenza G (2002) Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 64: 993–998

    Article  PubMed  CAS  Google Scholar 

  3. Gunaratnam L, Bonventre JV (2009) HIF in kidney disease and development. J Am Soc Nephrol 20: 1877–1887

    Article  PubMed  CAS  Google Scholar 

  4. Rosenberger C, Rosen S, Heyman S (2005) Current understanding of HIF in renal disease. Kidney Blood Press Res 28: 325–340

    Article  PubMed  Google Scholar 

  5. Willam C, Maxwell PH, Nichols L, et al (2006) HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligation. J Mol Cell Cardiol 41: 68–77

    Article  PubMed  CAS  Google Scholar 

  6. Li N, Yi F, Sundy CM, et al (2007) Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys. Am J Physiol Renal Physiol 292: F207–F216

    Article  PubMed  CAS  Google Scholar 

  7. Schodel J, Klanke B, Weidemann A, et al (2009) HIF-prolyl hydroxylases in the rat kidney: physiologic expression patterns and regulation in acute kidney injury. Am J Pathol 174: 1663–1674

    Article  PubMed  Google Scholar 

  8. Iguchi M, Kakinuma Y, Kurabayashi A, et al (2008) Acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in the mouse kidney. Nephron Exp Nephrol 110: e82–e90

    Article  PubMed  CAS  Google Scholar 

  9. Natarajan R, Salloum FN, Fisher BJ, Kukreja RC, Fowler III AA (2006) HIF-1 activation by prolyl 4-hyroxylase-2 gene silencing attenuates myocardial ischemia-reperfusion injury. Circ Res 98: 133–140

    Article  PubMed  CAS  Google Scholar 

  10. Rajagopalan S, Olin J, Deitcher S, et al (2007) Use of a constitutively active hypoxia-inducible factor-1alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients: phase I dose-escalation experience. Circulation 115: 1234–1243

    PubMed  CAS  Google Scholar 

  11. Myllyharju J (2009) HIF prolyl 4-hydroxylases and their potential as drug targets. Curr Pharm Des 15: 3878–3885

    Article  PubMed  CAS  Google Scholar 

  12. Nangaku M (2009) Novel therapeutic approach targeting the HIF-HRE system in the kidney. Adv Exp Med Biol 645: 81–86

    Article  PubMed  CAS  Google Scholar 

  13. Webb JD, Coleman ML, Pugh CW (2009) Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing. Cell Mol Life Sci 66: 3539–3554

    Article  PubMed  CAS  Google Scholar 

  14. Tanaka T, Wiesener M, Bernhardt W, Eckardt KU, Warnecke C (2009) The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J 424: 143–151

    Article  PubMed  CAS  Google Scholar 

  15. Callapina M, Zhou J, Schmid T, Kohl R, Brune B (2005) NO restores HIF-1alpha hydroxylation during hypoxia: role of reactive oxygen species. Free Radic Biol Med 39: 925–936

    Article  PubMed  CAS  Google Scholar 

  16. Haase VH (2006) The VHL/HIF oxygen-sensing pathway and its relevance to kidney disease. Kidney Int 69: 1302–1307

    PubMed  CAS  Google Scholar 

  17. Koivunen P, Hirsila M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J (2007) Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem 282: 4524–4532

    Article  PubMed  CAS  Google Scholar 

  18. Serra-Perez A, Planas AM, Nunez-O’Mara A, et al (2010) Extended ischemia prevents HIF1alpha degradation at reoxygenation by impairing prolyl-hydroxylation: role of Krebs cycle metabolites. J Biol Chem 285: 18217–1824

    Article  PubMed  CAS  Google Scholar 

  19. Rosenberger C, Rosen S, Heyman SN (2006) Renal Parenchymal Oxygenation and Hypoxia Adaptation in Acute Kidney Injury. Clin Exp Pharmacol Physiol 33: 980–988

    Article  PubMed  CAS  Google Scholar 

  20. Heyman SN, Khamaisi M, Rosen S, Rosenberger C (2008) Renal parenchymal hypoxia, hypoxia response and the progression of chronic kidney disease. Am J Nephrol 28: 998–1006

    Article  PubMed  CAS  Google Scholar 

  21. Rosenberger C, Mandriota S, Jurgensen JS, et al (2002) Expression of hypoxia-inducible factor-1alpha and-2alpha in hypoxic and ischemic rat kidneys. J Am Soc Nephrol 13: 1721–1732

    Article  PubMed  CAS  Google Scholar 

  22. Rosenberger C, Shina A, Rosen S, Goldfarb M, Eckardt K, Heyman SN (2006) Hypoxia inducible factors and tubular cell survival in isolated perfused kidneys. Kidney Int 70: 60–70

    Article  PubMed  CAS  Google Scholar 

  23. Rosenberger C, Heyman SN, Rosen S, et al (2005) Upregulation of HIF in acute renal failure — evidence for a protective transcriptional response to hypoxia. Kidney Int 67: 531–542

    Article  PubMed  CAS  Google Scholar 

  24. Paliege A, Rosenberger C, Bondke A, et al (2010) Hypoxia-inducible factor-2α-expressing interstitial fibroblasts are the only renal cells that express erythropoietin under hypoxiainducible factor stabilization. Kidney Int 77: 312–318

    Article  PubMed  CAS  Google Scholar 

  25. Rosenberger C, Griethe W, Gruber G, et al (2003) Cellular responses to hypoxia after renal segmental infarction. Kidney Int 64: 874–886

    Article  PubMed  Google Scholar 

  26. Rosenberger C, Goldfarb M, Shina A, et al (2008) Evidence for sustained renal hypoxia and transient hypoxia adaptation in experimental rhabdomyolysis-induced acute kidney injury. Nephrol Dial Transpl 23: 1135–1143

    Article  CAS  Google Scholar 

  27. Cursio R, Miele C, Filippa N, Van Obberghen E, Gugenheim J (2008) Liver HIF-1 alpha induction precedes apoptosis following normothermic ischemia-reperfusion in rats. Transplant Proc 40: 2042–2045

    Article  PubMed  CAS  Google Scholar 

  28. Heyman SN, Rosenberger C, Rosen S (2010) Experimental ischemia-reperfusion — biases and myths: the proximal vs. distal hypoxic tubular injury debate revisited. Kidney Int 77: 9–16

    Article  PubMed  Google Scholar 

  29. Goldfarb M, Rosenberger C, Abassi Z, et al (2006) Acute-on-chronic renal failure in the rat: Functional compensation and hypoxia tolerance. Am J Nephrol 26: 22–33

    Article  PubMed  Google Scholar 

  30. Rosenberger C, Khamaisi M, Abassi Z, et al (2008) Adaptation to hypoxia in the diabetic rat kidney. Kidney Int 73: 34–42

    Article  PubMed  CAS  Google Scholar 

  31. Rosenberger C, Pratschke J, Rudolph B, et al (2007) Immunohistochemical Detection of Hypoxia-Inducible Factor-1alpha in Human Renal Allograft Biopsies. J Am Soc Nephrol 18: 343–351

    Article  PubMed  CAS  Google Scholar 

  32. Hill P, Shukla D, Tran MG, et al (2008) Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury. J Am Soc Nephrol 19: 39–46

    Article  PubMed  CAS  Google Scholar 

  33. Jones NM, Lee EM, Brown TG, Jarrott B, Beart PM (2006) Hypoxic preconditioning produces differential expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its regulatory enzyme HIF prolyl hydroxylase 2 in neonatal rat brain. Neurosci Lett 404: 72–77

    Article  PubMed  CAS  Google Scholar 

  34. May D, Gilon D, Djonov V, et al (2008) Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proc Natl Acad Sci USA 105: 282–287

    Article  PubMed  CAS  Google Scholar 

  35. Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9: 677–684

    Article  PubMed  CAS  Google Scholar 

  36. Yang CC, Lin LC, Wu MS, Chien CT, Lai MK (2009) Repetitive hypoxic preconditioning attenuates renal ischemia/reperfusion induced oxidative injury via upregulating HIF-1 alpha-dependent bcl-2 signaling. Transplantation 88: 1251–1260

    Article  PubMed  CAS  Google Scholar 

  37. Hsieh MM, Linde NS, Wynter A, et al (2007) HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques. Blood 110: 2140–2147

    Article  PubMed  CAS  Google Scholar 

  38. Rosenberger C, Rosen S, Shina A, et al (2008) Activation of hypoxia inducible factors (HIF) ameliorates hypoxic distal tubular injury in the isolated perfused rat kidney. Nephrol Dial transplant 23: 3472–3478

    Article  PubMed  CAS  Google Scholar 

  39. Manotham K, Tanaka T, Ohse T, et al (2005) A biologic role of HIF-1 in the renal medulla. Kidney Int 67: 1428–1439

    Article  PubMed  CAS  Google Scholar 

  40. Bernhardt WM, Campean V, Kany S, et al (2006) Preconditional activation of hypoxiainducible factors ameliorates ischemic acute renal failure. J Am Soc Nephrol 17: 1970–1978

    Article  PubMed  CAS  Google Scholar 

  41. Bernhardt WM, Gottmann U, Doyon F, et al (2009) Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model. Proc Natl Acad Sci USA 106: 21276–21281

    Article  PubMed  CAS  Google Scholar 

  42. Weidemann A, Bernhardt WM, Klanke B, et al (2008) HIF activation protects from acute kidney injury. J Am Soc Nephrol 19: 486–494

    Article  PubMed  CAS  Google Scholar 

  43. Ockaili R, Natarajan R, Salloum F, et al (2005) HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation. Am J Physiol Heart Circ Physiol 289: H542–H548

    Article  PubMed  CAS  Google Scholar 

  44. Philipp S, Jurgensen JS, Fielitz J, et al (2006) Stabilization of hypoxia inducible factor rather than modulation of collagen metabolism improves cardiac function after acute myocardial infarction in rats. Eur J Heart Fail 8: 347–354

    Article  PubMed  CAS  Google Scholar 

  45. Kant R, Diwan V, Jaggi AS, Singh N, Singh D (2008) Remote renal preconditioninginduced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases. Mol Cell Biochem 312: 25–31

    Article  PubMed  CAS  Google Scholar 

  46. Zolk O, Solbach TF, Eschenhagen T, Weidemann A, Fromm MF (2008) Activation of negative regulators of the hypoxia-inducible factor (HIF) pathway in human end-stage heart failure. Biochem Biophys Res Commun 376: 315–320

    Article  PubMed  CAS  Google Scholar 

  47. Horowitz M, Assadi H (2010) Heat acclimation-mediated cross-tolerance in cardioprotection: do HSP70 and HIF-1alpha play a role? Ann N Y Acad Sci 1188: 199–206

    Article  PubMed  CAS  Google Scholar 

  48. Wu Y, Li X, Xie W, Jankovic J, Le W, Pan T (2010) Neuroprotection of deferoxamine on rotenone-induced injury via accumulation of HIF-1 alpha and induction of autophagy in SH-SY5Y cells. Neurochem Int 57: 198–205

    Article  PubMed  CAS  Google Scholar 

  49. Harten SK, Ashcroft M, Maxwell PH (2010) Prolyl hydroxylase domain inhibitors: a route to HIF activation and neuroprotection. Antioxid Redox Signal 12: 459–480

    Article  PubMed  CAS  Google Scholar 

  50. Niatsetskaya Z, Basso M, Speer RE, et al (2010) HIF prolyl hydroxylase inhibitors prevent neuronal death induced by mitochondrial toxins: therapeutic implications for Huntington’s disease and Alzheimer’s disease. Antioxid Redox Signal 12: 435–443

    Article  PubMed  CAS  Google Scholar 

  51. Siddiq A, Aminova LR, Troy CM, et al (2009) Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF-and CREB-independent pathways. J Neurosci 29: 8828–8838

    Article  PubMed  CAS  Google Scholar 

  52. Grover TR, Asikainen TM, Kinsella JP, Abman SH, White CW (2007) Hypoxia-inducible factors HIF-1alpha and HIF-2alpha are decreased in an experimental model of severe respiratory distress syndrome in preterm lambs. Am J Physiol Lung Cell Mol Physiol 292: L1345–L1351

    Article  PubMed  CAS  Google Scholar 

  53. Tajima T, Goda N, Fujiki N, et al (2009) HIF-1alpha is necessary to support gluconeogenesis during liver regeneration. Biochem Biophys Res Commun 387: 789–94

    Article  PubMed  CAS  Google Scholar 

  54. Milkiewicz M, Pugh CW, Egginton S (2004) Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice. J Physiol 2004 560: 21–26

    Article  CAS  Google Scholar 

  55. Rey S, Lee K, Wang CJ, et al (2009) Synergistic effect of HIF-1alpha gene therapy and HIF-1-activated bone marrow-derived angiogenic cells in a mouse model of limb ischemia. Proc Natl Acad Sci USA 106: 20399–20404

    Article  PubMed  CAS  Google Scholar 

  56. James LP, Donahower B, Burke AS, McCullough S, Hinson JA (2006) Induction of the nuclear factor HIF-1alpha in acetaminophen toxicity: evidence for oxidative stress. Biochem Biophys Res Commun 343: 171–176

    Article  PubMed  CAS  Google Scholar 

  57. Kang MJ, Kim HJ, Kim HK, et al (2005) The effect of age and calorie restriction on HIF-1-responsive genes in aged liver. Biogerontology 6: 27–37

    Article  PubMed  CAS  Google Scholar 

  58. Serchov T, Dubois-Pot-Schneider H, Charlot C, Rosl F, Wasylyk B (2010) Involvement of net and HIF-1alpha in distinct yet intricately linked hypoxia-induced signaling pathways. J Biol Chem 285: 21223–21232

    Article  PubMed  CAS  Google Scholar 

  59. Nechemia-Arbely Y, Rosenberger C, Khamaisi M, Koesters R, Shina A, Klaus S, Shriki A, Rosen S, Axelrod JH, Heyman SN (2009) Renal hypoxia inducible factors (HIF) and STAT3 cross-talk in vivo. J Am Soc Nephrol 20: F–FC184 (abst)

    Google Scholar 

  60. Jokilehto T, Jaakkola PM (2010) The role of HIF prolyl hydroxylases in tumour growth. J Cell Mol Med 14: 758–770

    Article  PubMed  CAS  Google Scholar 

  61. Higgins DF, Kimura K, Bernhardt WM, et al. (2007) Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest 117: 3810–3820

    PubMed  CAS  Google Scholar 

  62. Nevo O, Soleymanlou N, Wu Y, et al. (2006) Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol 291: R1085–R1093

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, Hadassah Hospital, Mt. Scopus, PO Box 24035, 91240, Jerusalem, Israel

    S. N. Heyman

  2. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard University, 330 Brookline Avenue, Boston, MA, 02215, USA

    S. Rosen

  3. Department of Nephrology, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    C. Rosenberger

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  1. S. N. Heyman
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  2. S. Rosen
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  3. C. Rosenberger
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Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Head) (Head)

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Heyman, S.N., Rosen, S., Rosenberger, C. (2011). Hypoxia-inducible Factors and the Prevention of Acute Organ Injury. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2011. Annual Update in Intensive Care and Emergency Medicine 2011, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18081-1_4

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  • DOI: https://doi.org/10.1007/978-3-642-18081-1_4

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