Anversa P, Olivetti G, Leri A, Liu Y, Kajstura J
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Curr Opin Nephrol Hypertens. 1997 Mar;6(2):169-76. doi: 10.1097/00041552-199703000-00011.
The recognition that cell death in the myocardium is not only necrotic in nature but is also mediated by activation of the suicide program of myocytes has raised several questions concerning the magnitude of this phenomenon, and whether these two distinct forms of cell death are disease-dependent or coexist in the pathologic heart. Additionally, the times required for the completion of apoptotic and necrotic myocyte cell death are unknown, making the analysis of their respective rates in the myocardium impossible at present. The documentation that mechanical forces in vitro, mimicking diastolic Laplace overloading in vivo, can transmit a death signal to myocytes suggests that programmed cell death may be triggered in the stressed myocardium independently from the etiology of the overload. Because increasing pressure or volume loads, or both, in the failing heart induce myocyte hypertrophy and proliferation, a challenging question is whether the induction of genes regulating these cellular growth processes may activate programmed cell death as well. Finally, the identification of the mechanisms responsible for the translation of a diffuse environmental condition into a death signal in a limited number of cells scattered across the ventricular wall is a major challenge of future research.
心肌细胞死亡不仅具有坏死性质，还可由心肌细胞自杀程序的激活介导，这一认识引发了几个问题，包括这种现象的程度，以及这两种不同形式的细胞死亡是否依赖于疾病，或者是否在病理性心脏中共存。此外，凋亡性和坏死性心肌细胞死亡完成所需的时间尚不清楚，使得目前无法分析它们在心肌中的各自速率。体外模拟体内舒张期拉普拉斯过载的机械力可将死亡信号传递给心肌细胞，这一证据表明，应激心肌中的程序性细胞死亡可能独立于过载的病因被触发。由于衰竭心脏中压力或容量负荷增加，或两者兼而有之，会诱导心肌细胞肥大和增殖，一个具有挑战性的问题是，调节这些细胞生长过程的基因的诱导是否也会激活程序性细胞死亡。最后，确定负责将弥漫性环境条件转化为散布在心室壁上有限数量细胞中的死亡信号的机制，是未来研究的一项重大挑战。
