Wilf Family Cardiovascular Research Institute, Departments of Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Circ Res. 2011 Apr 15;108(8):1017-36. doi: 10.1161/CIRCRESAHA.110.225730.
It is well known that apoptosis is an actively mediated cell suicide process. In contrast, necrosis, a morphologically distinct form of cell death, has traditionally been regarded as passive and unregulated. Over the past decade, however, experiments in Caenorhabditis elegans and mammalian cells have revealed that a significant proportion of necrotic death is, in fact, actively mediated by the doomed cell. Although a comprehensive understanding of necrosis is still lacking, some key molecular events have come into focus. Cardiac myocyte apoptosis and necrosis are prominent features of the major cardiac syndromes. Accordingly, the recognition of necrosis as a regulated process mandates a reexamination of cell death in the heart. This review discusses pathways that mediate programmed necrosis, how they intersect with apoptotic pathways, roles of necrosis in heart disease, and new therapeutic opportunities that the regulated nature of necrosis presents.
众所周知，细胞凋亡是一种主动介导的细胞自杀过程。相比之下，坏死作为一种形态上不同的细胞死亡形式，传统上被认为是被动和不受调节的。然而，在过去的十年中，秀丽隐杆线虫和哺乳动物细胞的实验表明，相当一部分坏死死亡实际上是由注定死亡的细胞主动介导的。尽管对坏死的全面理解仍有待提高，但一些关键的分子事件已经成为焦点。心肌细胞凋亡和坏死是主要心脏综合征的突出特征。因此，将坏死视为一种受调控的过程需要重新审视心脏中的细胞死亡。这篇综述讨论了介导程序性坏死的途径，它们如何与细胞凋亡途径交叉，坏死在心脏病中的作用，以及坏死的调控性质带来的新的治疗机会。
