Taking a load off: nuclear remodeling after mechanically supporting the failing human heart.
Taking a load off: nuclear remodeling after mechanically supporting the failing human heart.
复制标题
减轻负担：机械支撑衰竭的人类心脏后的核重塑。
DOI：
10.1161/cir.0b013e3181d61b63
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发表时间：
2010
期刊：
影响因子：
37.8
通讯作者：
Kühn,Bernhard
中科院分区：
文献类型：
--
作者：
Murry,CharlesE;Kühn,Bernhard
心脏通过改变其尺寸、形状、刚度、收缩性和电响应能力来适应不断变化的机械负荷，以满足新的需求。近年来，我们已经了解了大量关于增加负荷如何激活信号通路，从而导致调节分子、收缩蛋白、细胞外基质成分和离子通道表达变化的知识。 1 尽管这些通路最初具有适应性，但过度激活时可能会变得有害，导致心力衰竭。然而，人们不太认识到人类心肌细胞响应机械应力而启动细胞周期活动。例如，Adler 和 Friedburg 在 20 多年前就表明，机械负荷与核倍性（每个核 DNA 含量）的增加以及人类心肌细胞核数量的增加有关。 2 此外，一些研究小组已经发现疾病状态下心肌细胞 DNA 合成增加。 3 总之，这些数据表明，为了应对机械应力，分化的心肌细胞可以复制其 DNA，而无需经历核分裂（核分裂）或胞质分裂（细胞分裂），从而导致每个细胞的 DNA 含量更高。
The heart adapts exquisitely to changing mechanical loads by changing its size, shape, stiffness, contractility, and electric responsiveness to meet new demands. In recent years we have learned a great deal about how increased load activates signaling pathways that lead to changes in expression of regulatory molecules, contractile proteins, extracellular matrix components, and ion channels. 1 Although these pathways are initially adaptive, they can become deleterious when activated to excess, contributing to heart failure. It is less well recognized, however, that human cardiomyocytes initiate cell cycle activity in response to mechanical stress. For example, Adler and Friedburg showed more than 2 decades ago that mechanical loading is associated with increased nuclear ploidy (DNA content per nucleus) and with increased nuclear number in human cardiomyocytes. 2 Furthermore, several groups have identified increased cardiomyocyte DNA synthesis in disease states. 3 Together, these data suggest that, in response to mechanical stress, differentiated cardiomyocytes can replicate their DNA without undergoing karyokinesis (nuclear division) or cytokinesis (cell division), resulting in a higher DNA content per cell.