title: Myocardial apoptosis in a heterotopic murine heart transplantation model of chronic rejection and graft vasculopathy.
abstract: BACKGROUND
  Apoptosis has been implicated in myocardial reperfusion injury and in experimental transplantation rejection. One mechanism of apoptosis is through the interaction of the cell-surface Fas receptor on target cells and the Fas ligand that is expressed on cytotoxic T cells. The purpose of this study was to look for evidence of myocardial Fas receptor, Fas ligand, and apoptosis in a murine heterotopic heart transplantation model of chronic rejection/graft vasculopathy.
  
  
  METHODS
  Using the nick-end labeling technique, we examined a murine heterotopic heart transplantation model of chronic rejection/graft vasculopathy (strain B10.A to B10.BR) histologically for evidence of DNA fragmentation. MRNA for the Fas receptor, Fas ligand, and beta-actin was detected with reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Hearts harvested after 30 and 60 days showed an intimal index of the allografts (0.5 +/- 0.1) (mean +/- standard error) that was at least five times more than syngeneic grafts and native (nontransplanted) hearts (p < 0.01). In situ nick end-labeling of partially degraded DNA with terminal deoxynucleotydil transferase showed an increase in apoptotic cells in allografts and syngeneic grafts compared with native hearts. Reverse transcription-polymerase chain reaction detected equal myocardial RNA signal intensity of Fas receptor and beta-actin in allografts, syngeneic grafts, and native hearts. In contrast, allografts showed a strong signal for the Fas ligand mRNA, a signal not seen in syngeneic grafts or native hearts.
  
  
  CONCLUSIONS
  Apoptosis is occurring in both allografts and syngeneic grafts in this murine model of chronic rejection/graft vasculopathy, although distinct mechanisms may be involved.
authors.affiliation: Department of Surgery, University of Utah School of Medicine, Salt Lake City, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: White
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Shelby
authors.forename: M S
authors.initials: MS
authors.lastname: Trautman
authors.forename: S L
authors.initials: SL
authors.lastname: Perkins
authors.forename: E H
authors.initials: EH
authors.lastname: Hammond
authors.forename: R E
authors.initials: RE
authors.lastname: Shaddy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002908:Chronic Disease; D003327:Coronary Disease / Q000473:pathology*; D004249:DNA Damage; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000473:pathology*; D016027:Heart Transplantation / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000473:pathology*; D016042:Transplantation, Heterotopic / Q000473:pathology*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins