Cumulative Episodes of Rejection Altered Myocardial Sarcoplasmic Reticulum Ca2+-ATPase and Ryanodine Receptor-2 mRNA Expression in Heart Transplant Recipients

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The aim of the present study was to investigate the relationship between rejections and gene expression of Ca2+-handling proteins in heart transplant recipients. Thirty-seven heart transplant recipients underwent routine endomyocardial biopsy. Levels of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) and ryanodine receptor-2 mRNAs in endomyocardial tissue were quantified by a real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Rejections were diagnosed according to the conventional International Society for Heart and Lung Transplantation criteria. Patients were classified as follows; group AR+ (n = 9) with rejection grade of 2 or higher versus group AR- (n = 28) with rejection grade of 0, 1a or 1b at the time of biopsy, and group Rec-AR+ (n = 6) with a history of more than 4 episodes of treatment required rejection versus group Rec-AR- (n = 31) without history of recurrent rejection. The mRNA levels of the SERCA2/GAPDH ratio and ryanodine receptor-2/GAPDH ratio were not different between group AR+ and group AR-; however, they were reduced in group Rec-AR+ more than in group Rec-AR- (0.83 ± 0.07 versus 0.90 ± 0.07, P = 0.034, 0.74 ± 0.06 versus 0.84 ± 0.10, P = 0.027, respectively). A single episode of on-going rejection would not affect myocardial Ca2+-handling proteins; however, cumulative rejection episodes might alter the gene expression of myocardial Ca2+-handling proteins in heart transplant recipients.