title: Inflammatory genes in rat livers from cardiac- and brain death donors.
abstract: BACKGROUND
  Liver transplantation (LT) is the only life-saving treatment for patients with end-stage liver disease. The increase in patients has prompted the use of not only donation after brain death (DBD) donors but also living donors (LD) and donation after cardiac death (DCD) donors. Donor-type affects early graft function and graft survival as evidenced by an increased risk of developing ischemic type biliary lesions and higher risk of graft loss in DCD as compared with those in DBD grafts.
  
  
  METHODS
  Using a rat model, we used quantitative reverse transcription-polymerase chain reaction to examine expression levels of proinflammatory, cytoprotective, and injury genes and determined apoptosis in DCD and DBD livers at different time points after retrieval.
  
  
  RESULTS
  After retrieval, early mediators of inflammation MCP-1, HMGB1, and toll-like receptor (TLR 4) were increased in DCD livers, whereas the proinflammatory genes interleukin 6, interleukin 1β, tumor necrosis factor alpha, P-selectin, and E-selectin were massively upregulated in DBD compared with those in LD livers. HO-1 was increased in both postmortem groups. After cold ischemia, DCD livers showed increased levels of MCP-1, TLR4, and HMGB1, whereas expression of proinflammatory genes in DBD liver remained high. During 12 h of cold storage, expression levels remained stable except Hif-1α and HMGB1. DCD showed higher number of apoptotic cells compared with DBD livers.
  
  
  CONCLUSIONS
  Compared with LD, DCD livers showed only mild upregulation of inflammatory markers, but increased levels of MCP-1, HMGB1, and TLR4, and more apoptotic cells. In contrast, DBD livers showed a massive inflammatory response. These differences in tissue injury and inflammatory response might be relevant for the outcome after LT.
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Tanja C
authors.initials: TC
authors.lastname: Saat
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Denis
authors.initials: D
authors.lastname: Susa
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Niels F M
authors.initials: NF
authors.lastname: Kok
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: van den Engel
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Roest
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Jan N M
authors.initials: JN
authors.lastname: IJzermans
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: r.w.f.debruin@erasmusmc.nl.
authors.forename: Ron W F
authors.initials: RW
authors.lastname: de Bruin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001926:Brain Death / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D003643:Death; D024243:HMGB1 Protein / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D008099:Liver / Q000276:immunology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D014019:Tissue Donors; D051197:Toll-Like Receptor 4 / Q000235:genetics; D059467:Transcriptome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Cold ischemia; Deceased donors; Gene expression; Liver transplantation; Warm ischemia