title: Apoptotic myocardial cell death in the setting of arrhythmogenic right ventricular cardiomyopathy.
abstract: BACKGROUND
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive atrophy of the right ventricular myocardium accompanied by fibro-fatty replacement. We examined whether the loss of myocardial cells in the setting of ARVC could result from cell death by apoptosis as demonstrated by the detection of DNA fragmentation and the expression of apoptosis regulatory proteins (e.g. CPP-32, Bcl-2, and Bax).
  
  
  METHODS
  Specimens obtained from the right ventricular myocardium of 11 patients with ARVC (ARVC group) and 10 age-matched normal individuals (control group) were analysed. To identify individual cells undergoing apoptosis, paraffin sections were examined with the TdT-mediated dUTP-biotin nick end labelling method (TUNEL) and the rabbit polyclonal anti-single stranded DNA method (ssDNA). The apoptotic index was calculated as the percentage of nuclei staining positive by the TUNEL or ssDNA method. We also used immunohistochemical techniques to examine the levels of CPP-32, Bcl-2, and Bax expression.
  
  
  RESULTS
  Apoptosis was detected in the ARVC group with a mean apoptotic index of 5.7 +/- 4.5% (ssDNA) and 23.8 +/- 7.5% (TUNEL), but not in the control group (p < 0.01). CPP-32 expression and Bax overexpression were observed in the ARVC group. However, Bcl-2 expression was not seen in either group.
  
  
  CONCLUSIONS
  Apoptotic myocardial cell death occurs in the setting of ARVC and may contribute to the loss of myocardial cells.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Japan. ky26-nmu@m4.kcn.ne.jp
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaji
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Shinobu
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Chikao
authors.initials: C
authors.lastname: Yutani
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases