Evidence of Apoptosis in Arrhythmogenic Right Ventricular Dysplasia

BACKGROUND: Arrhythmogenic right ventricular dysplasia, a disorder that may lead to severe ventricular arrhythmias and sudden death, is characterized by the progressive replacement of myocardial cells by fat and fibrous tissue. We examined whether the loss of myocardial cells in this disease could result from cell death by apoptosis (programmed cell death). METHODS: Specimens obtained at autopsy from the right ventricular myocardium of eight patients with arrhythmogenic right ventricular dysplasia and four age-matched normal subjects were analyzed. To identify individual cells undergoing apoptosis, we performed in situ end-labeling of fragmented DNA on paraffin sections using biotinylated deoxyuridine triphosphate and the enzyme terminal deoxynucleotidyl transferase. We also examined the level of expression of CPP-32, a cysteine protease required for apoptotic cell death in mammalian cells, using immunohistochemical techniques. RESULTS: Apoptosis was detected in the right ventricular myocardium of six of the eight patients with arrhythmogenic right ventricular dysplasia and was absent in the controls. High levels of expression of CPP-32 were associated with positive in situ end-labeling of fragmented DNA. CONCLUSIONS: These results indicate that apoptotic myocardial cell death occurs in arrhythmogenic right ventricular dysplasia and may contribute to the loss of myocardial cells in this disorder.