Title: Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury
Authors: Hill, Peter
Shukla, Deepa
Tran, Maxine G. B
Aragones, Julian
Cook, H. Terence
Carmeliet, Peter
Maxwell, Patrick H # ×
Issue Date: Jan-2008
Publisher: Amer soc nephrology
Series Title: Journal of the american society of nephrology vol:19 issue:1 pages:39-46
Abstract: Acute renal failure resulting from hypoperfusion and hypoxia is a significant clinical problem. Hypoxia activates the heterodimeric transcription factor hypoxia inducible factor (HIF), leading to changes in gene expression that promote tissue adaptation and survival. To determine whether H IF may protect the kidney from ischemia-reperfusion injury, we subjected hif1a(+/-) and hif2a(+/-) mice to renal ischemia-reperfusion injury. Injury was substantially more severe in hif(+/-) than in littermate controls, consistent with a protective role for HIF. Because wild-type mice exhibited submaximal HIF accumulation in response to no-flow ischemia, we tested compounds that might augment the protective HIF response following ischemia-reperfusion in these animals. We found that L-Mimosine and dimethyloxalylglycine, two small molecules that activate HIF by inhibiting HIF hydroxylases, protected mouse kidneys from ischemia-reperfusion injury. Therefore, pharmacological activation of HIF may offer an effective strategy to protect the kidney from ischemic injury.
ISSN: 1046-6673
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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