Autophagy in load-induced heart disease.
Autophagy in load-induced heart disease.
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DOI：
10.1016/s0076-6879(08)04017-2
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发表时间：
2009
影响因子：
--
通讯作者：
Hill, Joseph A.
中科院分区：
文献类型：
--
作者：
Zhu, Hongxin;Rothermel, Beverly A.;Hill, Joseph A.
心脏是一个高度可塑的器官，能够根据生理或病理需求的变化进行重塑。当工作负荷增加时，心脏通过单个心肌细胞的肥大生长来补偿，以增加心输出量。然而，持续的压力，例如高血压或心肌梗塞后发生的压力，会引发肌节蛋白质组成和能量代谢的变化、心肌细胞的损失、心室扩张、泵功能降低，并最终导致心力衰竭。人们早就知道自噬在心肌细胞中活跃，在疾病中自噬水平升高。然而，心肌细胞自噬对心室重塑和疾病发病机制的潜在贡献直到最近才被探索。后一个事实很大程度上源于最近出现的工具来探测控制心脏可塑性的分子机制并定义自噬流在心脏病中的作用。在本章中，我们简要回顾了在负荷诱发的心脏病研究中有用的著名小鼠模型，以及用于评估分子或细胞事件是否适应或适应不良的标准技术。然后，我们概述了可用于监测心脏自噬活动的方法，为处理心脏和其他横纹肌的几种独特技术提供了详细的方案。
The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. When workload increases, the heart compensates through hypertrophic growth of individual cardiomyocytes to increase cardiac output. However, sustained stress, such as occurs with hypertension or following myocardial infarction, triggers changes in sarcomeric protein composition and energy metabolism, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Yet the potential contribution of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis has only recently been explored. This latter fact stems largely from the recent emergence of tools to probe molecular mechanisms governing cardiac plasticity and to define the role of autophagic flux in the context of heart disease. In this chapter, we briefly review prominent mouse models useful in the study of load-induced heart disease and standard techniques used to assess whether a molecular or cellular event is adaptive or maladaptive. We then outline methods available for monitoring autophagic activity in the heart, providing detailed protocols for several techniques unique to working with heart and other striated muscles.