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【medical-news】细胞自噬在负荷诱导的心血管疾病
The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. For example, when workload increases, compensatory hypertrophic growth of individual cardiomyocytes occurs to increase cardiac output. Sustained stress, however, such as that occurring with hypertension or following myocardial infarction, triggers changes in energy metabolism and sarcomeric protein composition, 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. Now, with recent advances in our understanding of molecular mechanisms governing autophagy, the potential contributions of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis are being explored. As part of this work, several recent studies have focused on autophagy in heart disease elicited by changes in hemodynamic load. Pressure overload stress elicits a robust autophagic response in cardiomyocytes that is maladaptive, contributing to disease progression. In this context, load-induced aggregation of intracellular proteins is a proximal event triggering autophagic clearance mechanisms. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction, where activation of autophagy is beneficial, antagonizing disease progression. Here, we review recent studies of cardiomyocyte autophagy in load-induced disease and address molecular mechanisms and unanswered questions.
Key Words: autophagy • cardiac hypertrophy • heart failure • hypertrophy • signal transduction
Circulation Research. 2008;103:1363 本人已认领该文献编译 48小时后如未提交 请其它战友自由认领 Autophagy in Load-Induced Heart Disease
细胞自噬在负荷诱导的心脏病中的作用
te heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. For example, when workload increases, compensatory hypertrophic growth of individual cardiomyocytes occurs to increase cardiac output. Sustained stress, however, such as that occurring with hypertension or following myocardial infarction, triggers changes in energy metabolism and sarcomeric protein composition, 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. Now, with recent advances in our understanding of molecular mechanisms governing autophagy, the potential contributions of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis are being explored. As part of this work, several recent studies have focused on autophagy in heart disease elicited by changes in hemodynamic load. Pressure overload stress elicits a robust autophagic response in cardiomyocytes that is maladaptive, contributing to disease progression. In this context, load-induced aggregation of intracellular proteins is a proximal event triggering autophagic clearance mechanisms. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction, where activation of autophagy is beneficial, antagonizing disease progression. Here, we review recent studies of cardiomyocyte autophagy in load-induced disease and address molecular mechanisms and unanswered questions.
心脏是个高度可塑性的器官，对于生理和病理性的损害有重塑的能力。比如，当心脏负荷加重，单个心肌细胞代偿性肥大来增加心输出量。但是，持续的压力，如高血压或心肌梗死之后出现的，导致心肌能量代谢和心肌纤维蛋白的组成的改变，心肌病的损失，心室扩张，泵功能降低最终导致心衰。已知某些时候自噬细胞在心肌病中激活，在疾病中增多。现在， 随着我们对分子机制控制的自噬作用的理解加深。心肌病自溶作用对于心室重塑及其疾病发病学的潜在作用被发现。 作为这项工作的一部分，几项近来的研究集中于通过改变血流动力学负荷来引出自溶作用在心脏病中作用。在心肌病中给予超负荷的压力引出强烈的自溶作用是不适当的，会导致疾病进展。本文中，负荷产生的细胞内蛋白质聚集是触发自噬作用清除机制的邻近事件。这些在超负荷压力下的发现与在蛋白质伴侣分子功能异常所诱发的蛋白质聚集的表现形成对比，后者自溶作用的激活是有利的，对抗疾病进程。这里，我们回顾近来在心肌病自溶作用在负荷产生的疾病中的研究，寻找其分子机制和尚未解决的问题。
y Words: autophagy • cardiac hypertrophy • heart failure • hypertrophy • signal transduction
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作者:admin@医学,生命科学 2011-03-27 17:11
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