Expression of heme oxygenase-1 in human livers before transplantation correlates with graft injury and function after transplantation.
Upregulation of heme oxygenase-1 (HO-1) has been proposed as an adaptive mechanism protecting against ischemia/reperfusion (I/R) injury. We investigated HO-1 expression in 38 human liver transplants and correlated this with I/R injury and graft function. Before transplantation, median HO-1 mRNA levels were 3.4-fold higher (range: 0.7-9.3) in donors than in normal controls. Based on the median value, livers were divided into two groups: low and high HO-1 expression. These groups had similar donor characteristics, donor serum transaminases, cold ischemia time, HSP-70 expression and the distribution of HO-1 promoter polymorphism. After reperfusion, HO-1 expression increased significantly further in the initial low HO-1 expression group, but not in the high HO-1 group. Postoperatively, serum transaminases were significantly lower and the bile salt secretion was higher in the initial low HO-1 group, compared to the high expression group. Immunofluorescence staining identified Kupffer cells as the main localization of HO-1. In conclusion, human livers with initial low HO-1 expression (<3.4 times controls) are able to induce HO-1 further during reperfusion and are associated with less injury and better function than initial high HO-1 expression (>3.4 times controls). These data suggest that an increase in HO-1 during transplantation is more protective than high HO-1 expression before transplantation.
Geuken
Erwin
E
Section Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands.
Buis
Carlijn I
CI
Visser
Dorien S
DS
Blokzijl
Hans
H
Moshage
Han
H
Nemes
Balazs
B
Leuvenink
Henri G D
HG
de Jong
Koert P
KP
Peeters
Paul M J G
PM
Slooff
Maarten J H
MJ
Porte
Robert J
RJ
D000328:Adult; D003080:Cold Temperature; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005787:Gene Frequency; D005838:Genotype; D006085:Graft Survival / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008099:Liver / Q000201:enzymology*; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control
D008565:Membrane Proteins; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1