title: Metabonomic analysis of rats with acute heart rejection.
abstract: BACKGROUND
  Organs transplantation is an effective treatment for end-stage organ failure. Despite the use of modern immunosuppressants to decrease its incidence, acute rejection episodes (ARE), still present a problem for diagnosis, resolution, and prediction of long-term outcomes due to the absence of sufficiently robust biomarkers.
  
  
  METHODS
  Using an heterotopic heart transplantation model using Dark Agouti to Lewis rats, and sirolimus (rapamycin, Rapa) treatment by gavage, we divided recipients into four groups: controls, ARE, Rapa-14, and Rapa-7. We evaluated recipients by hematoxylin and eosin staining of grafts and reverse transcription polymerase chain reactions. Levels of plasma metabolites were quantified using gas chromatography/time-of-flight mass spectrometry. Data were evaluated employing partial least-squares discriminant analysis (PLS-DA), the area under the receiver operating characteristic curves with negative predictive values (NPV) and positive predictive values (PPV).
  
  
  RESULTS
  The graft survival was prolonged by Rapa. Plasma levels of 10 metabolites differed significantly between the ARE and the Rapa-14 groups as illustrated by the total ion current. According to PLS-DA, proline, glycine, serine, phenylalanine, and isocitrate showed the greatest effects with areas under the curve of 0.944, 0.917, 1.0, 0.861, and 0.944 respectively. The NPV values were 85.7%, 85.7%, 100%, 83.3%, and 85.7% and PPV values, 100%, 100%, 100%, 83.3%, and 100% respectively. Therefore, these metabolites may be used to predict the occurrence and progression of ARE.
  
  
  CONCLUSIONS
  The trend of changes suggested that plasma metabolites correlated with the immune state of recipients. Therefore, metabonomics may provide new biomarkers for graft injury in the early phases of ARE.
authors.affiliation: Department of General Surgery, Peking University Third Hospital, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Tao
authors.forename: D R
authors.initials: DR
authors.lastname: Xiu
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016002:Discriminant Analysis; D008401:Gas Chromatography-Mass Spectrometry; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016018:Least-Squares Analysis; D008297:Male; D055432:Metabolomics / Q000379:methods; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D012372:ROC Curve; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D020123:Sirolimus