RESUMO
Objective Allograft 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 the metabolism of branched-chain amino acids (BCAA). Methods The 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.Results All 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 E1 a, 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 blool vessels with cardiac allograft vasculopathy (CAV).BCAA concentrations were increased in the cardiac allografts, but there was no difference in the serum. Conclusion These findings suggest that the catabolic pathways of the BCAA may be inhibited owing to the reduced expression of BCKDH complex, and elevated intracellular concentrations of leucine. The vascular smooth muscle cell and cardiac muscle cell proliferation is stimulated via mTOR-dependent and mTOR-independent pathways, which is associated with the formation of myocardial hypertrophy and AV in the heart allografts.
