title: The hypoxia-inflammation link and potential drug targets.
abstract: OBJECTIVE
  Hypoxia represents one of the strongest transcriptional stimuli known to us. In most cases, hypoxia-induced changes in gene expression are directed towards adapting tissues to conditions of limited oxygen availability.
  
  
  RESULTS
  As a well known example, physical exercise at high altitude results in the transcriptional induction of erythropoietin that functions to increase oxygen carrying capacity and red cell volume. Studies of the transcriptional pathway responsible for the induction of erythropoietin during conditions of hypoxia led to the discovery of the transcription factor hypoxia-inducible factor (HIF) that is known today as the key transcription factor for hypoxia adaptation. Surgical patients are frequently at risk for experiencing detrimental effects of hypoxia or ischemia, for example, in the context of acute kidney injury, myocardial, intestinal or hepatic ischemia, acute lung injury, or during organ transplantation.
  
  
  CONCLUSIONS
  In the present review, we discuss the mechanisms of transcriptional adaptation to hypoxia and provide evidence supporting the hypothesis that targeting hypoxia-induced inflammation can represent novel pharmacologic strategies to improve perioperative outcomes. Currently, such strategies are being explored at an experimental level, but we hope that some of these targets can be translated into perioperative patient care within the next decade.
authors.affiliation: Mucosal Inflammation Program, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Koeppen
authors.forename: Tobias
authors.initials: T
authors.lastname: Eckle
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D015398:Signal Transduction
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011393:Procollagen-Proline Dioxygenase