Authors
Martin Schneider, Katie Van Geyte, Peter Fraisl, Judit Kiss, Julián Aragonés, Massimiliano Mazzone, Heimo Mairbäurl, Katrien De Bock, Nam Ho Jeoung, Martin Mollenhauer, Maria Georgiadou, Tammie Bishop, Carmen Roncal, Andrew Sutherland, Benedicte Jordan, Bernard Gallez, Jürgen Weitz, Robert A Harris, Patrick Maxwell, Myriam Baes, Peter Ratcliffe, Peter Carmeliet
Publication date
2010/3/1
Journal
Gastroenterology
Volume
138
Issue
3
Pages
1143-1154. e2
Publisher
WB Saunders
Description
BACKGROUND & AIMS
Liver ischemia/reperfusion (I/R) injury is a frequent cause of organ dysfunction. Loss of the oxygen sensor prolyl hydroxylase domain enzyme 1 (PHD1) causes tolerance of skeletal muscle to hypoxia. We assessed whether loss or short-term silencing of PHD1 could likewise induce hypoxia tolerance in hepatocytes and protect them against hepatic I/R damage.
METHODS
Hepatic ischemia was induced in mice by clamping of the portal vessels of the left lateral liver lobe; 90 minutes later livers were reperfused for 8 hours for I/R experiments. Hepatocyte damage following ischemia or I/R was investigated in PHD1-deficient (PHD1−/−) and wild-type mice or following short hairpin RNA-mediated short-term inhibition of PHD1 in vivo.
RESULTS
PHD1−/− livers were largely protected against acute ischemia or I/R injury. Among mice subjected to hepatic I/R followed by surgical resection of all …
Total citations
Scholar articles
M Schneider, K Van Geyte, P Fraisl, J Kiss, J Aragonés… - Gastroenterology, 2010