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

Tomoko S. Kato; Kazuo Komamura; Yusuke Sata; Hatsue Ishibashi-Ueda; Yoshihiko Ikeda; Taka-aki Matsuyama; Hideo Izawa; Mitsuhiro Yokota; Toshiaki Shishido; Takeshi Nakatani; Soichiro Kitamura; Masaki Asakura; Kazuhiko Hashimura; Masafumi Kitakaze

doi:10.1536/ihj.51.259

Clinical Studies

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

Tomoko S. Kato, Kazuo Komamura, Yusuke Sata, Hatsue Ishibashi-Ueda, Yoshihiko Ikeda, Taka-aki Matsuyama, Hideo Izawa, Mitsuhiro Yokota, Toshiaki Shishido, Takeshi Nakatani, Soichiro Kitamura, Masaki Asakura, Kazuhiko Hashimura, Masafumi Kitakaze

Author information

Tomoko S. Kato
Department of Cardiovascular Medicine, National Cardiovascular Center
Department of Organ Transplantation, National Cardiovascular Center
Kazuo Komamura
Department of Cardiovascular Medicine, National Cardiovascular Center
Department of Organ Transplantation, National Cardiovascular Center
Yusuke Sata
Department of Cardiovascular Medicine, National Cardiovascular Center
Hatsue Ishibashi-Ueda
Department of Pathology, National Cardiovascular Center
Yoshihiko Ikeda
Department of Pathology, National Cardiovascular Center
Taka-aki Matsuyama
Department of Pathology, National Cardiovascular Center
Hideo Izawa
Department of Cardiology, Fujita Health University School of Medicine
Mitsuhiro Yokota
Department of Genome Science, Aichi-Gakuin University School of Dentistry
Toshiaki Shishido
Department of Cardiovascular Dynamics, National Cardiovascular Center
Takeshi Nakatani
Department of Organ Transplantation, National Cardiovascular Center
Soichiro Kitamura
Department of Cardiovascular Surgery, National Cardiovascular Center
Masaki Asakura
Department of Cardiovascular Medicine, National Cardiovascular Center
Kazuhiko Hashimura
Department of Cardiovascular Medicine, National Cardiovascular Center
Masafumi Kitakaze
Department of Cardiovascular Medicine, National Cardiovascular Center

Keywords: Transplantation, Gene expression, Biopsy, Sarcoplasmic reticulum

JOURNAL FREE ACCESS

2010 Volume 51 Issue 4 Pages 259-263

DOI https://doi.org/10.1536/ihj.51.259

Details

Abstract

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.

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