Ultrastructural definition of apoptosis in heart failure
Ultrastructural definition of apoptosis in heart failure
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DOI：
10.1007/s10741-007-9072-8
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发表时间：
2008-06-01
影响因子：
4.6
通讯作者：
Narula, Jagat
中科院分区：
文献类型：
--
作者：
Arbustini, Eloisa;Brega, Agnese;Narula, Jagat
心肌细胞通过凋亡、胀亡和自噬死亡。细胞凋亡影响单个细胞，其形态学特征为核碎裂，并产生凋亡小体，凋亡小体可在垂死细胞内或在间质空间中游离。死亡的肌细胞被巨噬细胞通过吞噬作用清除，而不会引发炎症。心肌细胞坏死的循环标志物不因细胞凋亡而增加。诱导和早期执行阶段的形态变化在电子显微镜下观察到，而后期的碎片在光学显微镜和电子显微镜下都可见。免疫电子显微镜提供了组合的功能和结构信息，显示细胞色素c免疫标记从线粒体释放，凋亡细胞核的TUNEL标记，膜联蛋白V易位在外浆细胞层。胀亡的特点是特定的形态学特征，可能与凋亡共存，特别是在缺血心肌。自噬是一种防御过程，当溶酶体内容物的去除受损时，自噬与显著的心肌损伤和坏死相关。细胞凋亡、细胞胀亡和细胞自噬的形态学特征可能同时并存。虽然死亡的心肌细胞显示的自噬和凋亡的特点是很少观察到在人类失代偿的心脏，自噬空泡，和早期凋亡的变化可能会看到更多的形态学上可行的心肌细胞。此类特征可能发生在缺血性和非缺血性病因的衰竭心脏中。在不同病因的衰竭人类心脏中心肌细胞死亡的共同模式表明，通过类似的治疗策略，心肌细胞完整性的保护是可能的。
Cardiac myocytes die through apoptosis, oncosis, and autophagy. Apoptosis affects single cells and is morphologically characterized by nuclear fragmentation with generation of apoptotic bodies that can be seen either within dying cells or free in the interstitial spaces. Dead myocytes are removed by macrophages through phagocytosis without triggering inflammation. The circulating markers of myocyte necrosis are not increased by apoptosis. The morphologic changes of the induction and early execution phases are seen at electron microscopy while late fragmentation is visible on both light and electron microscopy. Immunoelectron microscopy provides combined functional and structural information showing cytochrome c immuno-labelling release from mitochondria, TUNEL labelling of apoptotic nuclei, annexin V translocation in the outer plasma cell layer. Oncosis is characterized by specific morphologic features that may coexist with apoptosis, especially in ischemic myocardium. Autophagy is a defense process that is associated with significant myocardial damage and necrosis when removal of the lysosomal content is impaired. Morphological features of apoptosis, oncosis, and autophagocytosis may coexist at the same time. Although dead myocytes showing characteristics of autophagy and apoptosis are rarely observed in human decompensated hearts, autophagic vacuoles, and early apoptotic changes may be seen more often in morphologically viable myocytes. Such features may occur in failing hearts of both ischemic and non-ischemic etiology. The shared mode of cardiac myocyte death in failing human hearts of different etiologies suggests that preservation of myocyte integrity may be possible by similar therapeutic strategies.