PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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: Balázs Csóka; Zoltán H Németh; Peter Rosenberger; Holger K Eltzschig; Zoltán Spolarics; Pál Pacher; Zsolt Selmeczy; Balázs Koscsó; Leonóra Himer; E Sylvester Vizi; Michael R Blackburn; Edwin A Deitch; György Haskó Journal: J Immunol Date: 2010-05-26 Impact factor: 5.422
Authors: Almut Grenz; Julee H Dalton; Jessica D Bauerle; Alexander Badulak; Douglas Ridyard; Aneta Gandjeva; Carol M Aherne; Kelley S Brodsky; Jae-Hwan Kim; Rubin M Tuder; Holger K Eltzschig Journal: PLoS One Date: 2011-05-19 Impact factor: 3.240
Authors: J Armstrong-Wells; M D Post; M Donnelly; M J Manco-Johnson; B M Fisher; V D Winn Journal: J Dev Orig Health Dis Date: 2013-06 Impact factor: 2.401
Authors: Tingting Weng; Harry Karmouty-Quintana; Luis J Garcia-Morales; Jose G Molina; Mesias Pedroza; Raquel R Bunge; Brian A Bruckner; Matthias Loebe; Harish Seethamraju; Michael R Blackburn Journal: FASEB J Date: 2013-02-07 Impact factor: 5.191
Authors: Eunyoung Tak; Douglas Ridyard; Alexander Badulak; Antasia Giebler; Uladzimir Shabeka; Tilmann Werner; Eric Clambey; Radu Moldovan; Michael A Zimmerman; Holger K Eltzschig; Almut Grenz Journal: J Mol Med (Berl) Date: 2013-05-01 Impact factor: 4.599