Mallat Z, Tedgui A, Fontaliran F, Frank R, Durigon M, Fontaine G
Centre de Rythmologie et de Stimulation Cardiaque, Hôpital Jean Rostand, Ivry-sur-Seine, France.
N Engl J Med. 1996 Oct 17;335(16):1190-6. doi: 10.1056/NEJM199610173351604.
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).
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.
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.
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.
致心律失常性右室发育不良是一种可能导致严重室性心律失常和猝死的疾病，其特征是心肌细胞逐渐被脂肪和纤维组织替代。我们研究了该疾病中心肌细胞的丢失是否由凋亡（程序性细胞死亡）导致的细胞死亡引起。
分析了8例致心律失常性右室发育不良患者及4例年龄匹配的正常受试者尸检时获取的右室心肌标本。为识别正在发生凋亡的单个细胞，我们使用生物素化的脱氧尿苷三磷酸和末端脱氧核苷酸转移酶对石蜡切片上的断裂DNA进行原位末端标记。我们还使用免疫组化技术检测了CPP-32的表达水平，CPP-32是哺乳动物细胞凋亡性细胞死亡所需的一种半胱氨酸蛋白酶。
8例致心律失常性右室发育不良患者中有6例的右室心肌检测到凋亡，而对照组未检测到。CPP-32的高表达与断裂DNA原位末端标记阳性相关。
这些结果表明，凋亡性心肌细胞死亡发生在致心律失常性右室发育不良中，可能导致该疾病中心肌细胞的丢失。
