Microarray-based Gene Expression Profiling of Retransplanted Rat Cardiac Allografts That Develop Cardiac Allograft Vasculopathy

We studied the expression of 9,906 genes in retransplanted rat cardiac allografts that developed cardiac allograft vasculopathy (CAV) with the use of DNA microarray and real-time reverse transcriptase-polymerase chain reaction. Although only a slight difference in the timing of the retransplantation induced the later development of CAV, 1,067 genes were differentially expressed in the allografts 1 day after retransplantation. Thus, the development of CAV was determined by a robust difference in gene expression soon after retransplantation, controlled by a slight difference in retransplantation timing. In contrast, only 26 genes showed significant upregulation in the later phase of CAV development, and the time-course of the induction of 16 genes was associated with CAV progression. Of these genes, 8 were induced in 2 different aortic allograft combinations, and the time-course of the induction was correlated with the development of transplant vasculopathy. Microarray-based gene expression profiling has the potential to elucidate the mechanism of experimental chronic cardiac allograft rejection.