Zhang Qingchu(章慶春，Dept Cardiac Surg，Anhui Provin Hosp，Hefei 230001)…∥Chin J Organ Transplant.－ 2011，32(8).－492～496

Dysfunction of branded－chain amino acids catabolism in rat cardiac allograft

Zhang Qingchu(章慶春，Dept Cardiac Surg，Anhui Provin Hosp，Hefei 230001)…∥Chin J Organ Transplant.－ 2011，32(8).－492～496

ObjectiveAllograft vasculopathy(AV)，feature of chronic rejection，is a major serious long－term post－operation complication in organ transplantation.The accurate mechanisms for AV have not been definitively established，but extensive basic and clinical studies demonstrate AV is triggered by immune reaction and nonimmunologic factors，and also possibly attributed to metabolism of branched－chain amino acids(BCAA).MethodsThe transplanted hearts from Lewis to Sprague－Dawely rats served as allografts and those from Lewis to Lewis rats as isografts based on Ono＇s model.The differential proteins in transplanted hearts were separated by comparative proteomic technique，and some enzymes which regulated the metabolism of BCAA were identified and validated.ResultsAll transplanted hearts at second week postoperation were characterized by lumen loss(total area－luminal area/total area)in coronary artery，but more predominant at 8th week.All samples from the left ventricles were analyzed by proteomic techniques and the subunits E1α，E1β and E3 of branched－chain α －ketoacid dehydrogenase(BCKDH)complex were decreased in the heart allografts.Immunohistological detection also showed the expression of BCKDH was reduced not only in the cardiac muscle but also more significantly in blood vessels with cardiac allograft vasculopathy(CAV).BCAA concentrations wereincreased in cardiacallografts，but there was no difference in serum.ConclusionThese findings suggest that catabolic pathways of BCAA may be inhibited owing to reduced expression of BCKDH complex，and elevated intracellular concentrations of leucine.Vascular smooth muscle cell and cardiac muscle cell proliferation is stimulated via mTOR－dependent and mTOR －independent pathways，hypertrophy and AV in heart allografts.15 refs，4 figs，2 tabs.

(Authors)