Apoptosis in myocytes in end-stage heart failure
Apoptosis in myocytes in end-stage heart failure
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DOI：
10.1056/nejm199610173351603
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发表时间：
1996-10-17
影响因子：
158.5
通讯作者：
Khaw, BA
中科院分区：
文献类型：
--
作者：
Narula, J;Haider, N;Khaw, BA
背景心力衰竭可由多种原因引起，包括缺血性、高血压、中毒性和炎症性心脏病。然而，心力衰竭时心肌功能进行性恶化的细胞机制尚不清楚，可能是细胞凋亡(程序性细胞死亡)所致。方法我们检查了7例心脏移植患者的移植心脏，所有患者都有严重的慢性心力衰竭，其中4例为特发性扩张型心肌病，3例为缺血性心肌病，DNA片段化(细胞凋亡的标志)通过原位末端标记和末端标记DNA的琼脂糖凝胶电泳法进行组织化学鉴定。结果4例特发性扩张型心肌病患者和1例缺血性心肌病患者的心脏组织均有DNA片段化的组织化学证据，4例扩张型心肌病患者的心脏标本均有DNA片段化，4例扩张型心肌病患者的心肌标本均出现DNA梯状条带，这是一种细胞凋亡的特征，而缺血性心肌病患者的心脏标本均未见DNA梯状条带。在急性心肌梗死的中央坏死区也观察到了细胞凋亡的组织学证据，但在远离梗死区的心肌中没有观察到细胞凋亡。结论终末期心肌病患者心肌细胞因细胞凋亡而丢失，可能与进展性心肌功能障碍有关。(C)1996年，马萨诸塞州医学会。
Background Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death).Methods We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis, All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy, DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from Sour persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies.Results Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation, All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histologic evidence of apoptosis was also observed in the central necrotic zone of acute myocardial infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents.Conclusions Loss of myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction. (C) 1996, Massachusetts Medical Society.