Metabolomics identifies metabolite biomarkers associated with acute rejection after heart transplantation in rats

• Published in: Scientific reports 2017-11, Vol.7 (1), p.15422-10, Article 15422
• Main Authors: Lin, Feng, Ou, Yi, Huang, Chuan-Zhong, Lin, Sheng-Zhe, Ye, Yun-Bin
• Format: Article
• Language: English
• Subjects: 631/61/320; 692/699/75; Animals; Biomarkers; Biomarkers - metabolism; Biopsy; Choline; Chromatography, High Pressure Liquid - methods; D-tagatose; Disease Models, Animal; Glutamine; Graft rejection; Graft Rejection - blood; Graft Rejection - diagnosis; Graft Rejection - metabolism; Graft Rejection - pathology; Heart; Heart diseases; Heart transplantation; Heart Transplantation - adverse effects; Humanities and Social Sciences; Humans; Liver; Lung transplantation; Male; Metabolites; Metabolomics; Metabolomics - methods; multidisciplinary; Myocardium - pathology; Predictive Value of Tests; Prognosis; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rodents; Science; Science (multidisciplinary); Spectrometry, Mass, Electrospray Ionization - methods; Sphinganine; Tandem Mass Spectrometry - methods; Transplantation; Transplantation, Homologous - adverse effects; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-15761-3

The aim of this study was to identify metabolite biomarkers associated with acute rejection after heart transplantation in rats using a LC-MS-based metabolomics approach. A model of heterotopic cardiac xenotransplantation was established in rats, with Wistar rats as donors and SD rats as recipients. Blood and cardiac samples were collected from blank control rats (Group A), rats 5 (Group B) and 7 days (Group C) after heart transplantation, and pretreated rats 5 (Group D) and 7 days (Group E) post-transplantation for pathological and metabolomics analyses. We assessed International Society for Heart and Lung Transplantation (ISHLT) grades 0, 3B, 4, 1 and 1 rejection in groups A to E. There were 15 differential metabolites between groups A and B, 14 differential metabolites between groups A and C, and 10 differential metabolites between groups B and C. In addition, four common differential metabolites, including D-tagatose, choline, C16 sphinganine and D-glutamine, were identified between on days 5 and 7 post-transplantation. Our findings demonstrate that the panel of D-tagatose, choline, C16 sphinganine and D-glutamine exhibits a high sensitivity and specificity for the early diagnosis of acute rejection after heart transplantation, and LC-MS-based metabolomics approach has a potential value for screening post-transplantation biomarkers.