title: Decrease in donor heart injury by recombinant clusterin protein in cold preservation with University of Wisconsin solution.
abstract: BACKGROUND
  Donor organ injury during cold preservation before transplantation negatively impacts graft survival. Clusterin (CLU) is a chaperonic protein, and its expression confers donor hearts resistance to cold ischemic injury. This study was conducted to evaluate if the supplement of recombinant CLU protein (rCLU) protects donor organs from injury during cold storage with University of Wisconsin (UW) solution.
  
  
  METHODS
  Human endothelial cell cultures were used as an in vitro model. Heart transplantation in mice was used as an in vivo model. Cell membrane disruption or death was indicated by the release of lactate dehydrogenase (LDH). Donor injury was determined by its functional recovery, and histologic and biochemical analyses.
  
  
  RESULTS
  Supplement of rCLU to UW solution protected cultured human endothelial cells from cold-induced cell necrosis, as evidenced by a decrease in both release of LDH and the number of ethidium bromide-stained necrotic cells. The protective activity of rCLU was associated with enhanced membrane fluidity at cold temperature. During cold storage of heart organs in UW solution, supplemental rCLU significantly decreased LDH release from heart tissue. In a preclinical model of transplantation, heart grafts after cold preservation with rCLU-containing UW solution had better functional recovery and decreased perivascular inflammation, neutrophil infiltration, and cardiac cell death, including apoptosis and necrosis, that correlated with lower levels of serum creatine kinase and LDH in recipients.
  
  
  CONCLUSIONS
  Our data suggest that supplement of CLU protein in a cold preservation solution may have potential in improving cold preservation of donor organs in transplantation.
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, and the Vancouver Prostate Centre, Vancouver, BC, Canada.
authors.forename: Qiunong
authors.initials: Q
authors.lastname: Guan
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Li
authors.forename: Gordon
authors.initials: G
authors.lastname: Yip
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Christopher Y C
authors.initials: CY
authors.lastname: Nguan
authors.forename: Caigan
authors.initials: C
authors.lastname: Du
mesh_terms: D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051152:Clusterin / Q000494:pharmacology*; D050377:Cold Ischemia; D005978:Glutathione; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000379:methods* / Q000473:pathology / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007328:Insulin; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011887:Raffinose; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C495242:CLU protein, human; D002316:Cardiotonic Agents; D051152:Clusterin; D007328:Insulin; D019188:Organ Preservation Solutions; D011994:Recombinant Proteins; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose