Oxidative Stress and Endothelial Dysfunction during Sepsis

  • O. Huet
  • A. Harrois
  • J. Duranteau


The endothelium is an active tissue that plays a pivotal role in maintaining cardiovascular homeostasis. The endothelium ensures the quality of both the global and microcirculation. It forms an interface between blood and tissues. The human body contains approximately 1013 endothelial cells, an area of 4000 to 7000 m2. This size is one of the reasons why endothelium must be considered an organ. Physiological functions of endothelial cells are: 1) to control vascular tone and blood flow by a local balance between vasodilators (paracrine release of diffusible vasodilator mediators, such as nitric oxide [NO], prostacyclin) and vasopressors (endothelin-1 [ET-1]); 2) to keep blood in a fluid state by preventing thrombosis; 3) to control the exchange of fluid and macromolecules between the blood and the tissues; and 4) to control the local balance between pro- and anti-inflammatory mediators.


Septic Shock Endothelial Dysfunction Human Umbilical Vein Endothelial Cell Mitochondrial Respiratory Chain Reactive Nitrogen Species 
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.


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  1. 1.
    Halliwell B, Zhao K, Whiteman M (1999) Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies. Free Radic Res 31: 651–669CrossRefPubMedGoogle Scholar
  2. 2.
    Budinger GR, Duranteau J, Chandel NS, Schumacker PT (1998) Hibernation during hypoxia in cardiomyocytes. Role of mitochondria as the O2 sensor. J Biol Chem 273: 3320–3326CrossRefPubMedGoogle Scholar
  3. 3.
    Cerwinka WH, Cooper D, Krieglstein CF, Ross CR, McCord JM, Granger DN (2003) Superoxide mediates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules. Am J Physiol Heart Circ Physiol 284:H535–541Google Scholar
  4. 4.
    Sikora JP (2002) Immunotherapy in the management of sepsis. Arch Immunol Ther Exp (Warsz) 50: 317–324Google Scholar
  5. 5.
    Fialkow L, Wang Y, Downey GP (2007) Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med 42: 153–164CrossRefPubMedGoogle Scholar
  6. 6.
    Therade-Matharan S, Laemmel E, Carpentier S, et al (2005) Reactive oxygen species production by mitochondria in endothelial cells exposed to reoxygenation after hypoxia and glucose depletion is mediated by ceramide. Am J Physiol Regul Integr Comp Physiol 289:R1756–1762PubMedGoogle Scholar
  7. 7.
    Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT (1998) Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem 273: 11619–11624CrossRefPubMedGoogle Scholar
  8. 8.
    Corda S, Laplace C, Vicaut E, Duranteau J (2001) Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am J Respir Cell Mol Biol 24: 762-768Google Scholar
  9. 9.
    Huet O, Obata R, Aubron C, et al (2007) Plasma-induced endothelial oxidative stress is related to the severity of septic shock. Crit Care Med 35: 821–826CrossRefPubMedGoogle Scholar
  10. 10.
    Chung HY, Yokozawa T, Kim MS, et al (2000) The mechanism of nitric oxide and/or superoxide cytotoxicity in endothelial cells. Exp Toxicol Pathol 52: 227–233PubMedGoogle Scholar
  11. 11.
    Brown GC, Borutaite V (1999) Nitric oxide, cytochrome c and mitochondria. Biochem Soc Symp 66: 17–25PubMedGoogle Scholar
  12. 12.
    Huet O, Cherreau C, Nicco C, et al (2008) Pivotal role of glutathione depletion in plasma-induced endothelial oxidative stress during sepsis. Crit Care Med 36: 2328–2334CrossRefPubMedGoogle Scholar
  13. 13.
    Li H, Forstermann U (2000) Nitric oxide in the pathogenesis of vascular disease. J Pathol 190: 244–254CrossRefPubMedGoogle Scholar
  14. 14.
    Radi R, Cassina A, Hodara R (2002) Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem 383: 401–409CrossRefPubMedGoogle Scholar
  15. 15.
    Thum T, Fraccarollo D, Schultheiss M, et al (2007) Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes. Diabetes 56: 666–674CrossRefPubMedGoogle Scholar
  16. 16.
    Gao YT, Roman LJ, Martasek P, Panda SP, Ishimura Y, Masters BS (2007) Oxygen metabolism by endothelial nitric-oxide synthase. J Biol Chem 282: 28557–28565CrossRefPubMedGoogle Scholar
  17. 17.
    Sullivan JC, Pollock JS (2006) Coupled and uncoupled NOS: separate but equal? Uncoupled NOS in endothelial cells is a critical pathway for intracellular signaling. Circ Res 98: 717–719CrossRefPubMedGoogle Scholar
  18. 18.
    Ince C (2004) Microcirculation in distress: a new resuscitation end point? Crit Care Med 32: 1963–1964CrossRefPubMedGoogle Scholar
  19. 19.
    Li JM, Shah AM (2004) Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol 287:R1014–1030PubMedGoogle Scholar
  20. 20.
    Rada BK, Geiszt M, Kaldi K, Timar C, Ligeti E (2004) Dual role of phagocytic NADPH oxidase in bacterial killing. Blood 104: 2947–2953CrossRefPubMedGoogle Scholar
  21. 21.
    Cadenas E (2004) Mitochondrial free radical production and cell signaling. Mol Aspects Med 25: 17–26CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • O. Huet
    • 1
  • A. Harrois
    • 1
  • J. Duranteau
    • 1
  1. 1.Department of Anesthesia and Surgical Intensive CareCHU de BicêtreLe Kremlin Bicêtre CedexFrance

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