Myocardial stress and autophagy: mechanisms and potential therapies.
Myocardial stress and autophagy: mechanisms and potential therapies.
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DOI：
10.1038/nrcardio.2017.35
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Gottlieb RA
中科院分区：
文献类型：
--
作者：
Delbridge LMD;Mellor KM;Taylor DJ;Gottlieb RA
自噬是一种普遍存在的细胞对能量应激的反应。过去十年的研究表明，心肌细胞自噬是一种重要的稳态途径，在适应改变的心肌代谢需求方面很重要。自噬的细胞机制涉及大分子和细胞器的定向降解。自噬激活已被确定为在某些情况下的心脏保护（即缺血和缺血预处理）。在其他情况下，自噬水平的长期升高与心脏病理学（即持续的压力超负荷和衰竭）有关。糖尿病性心肌病中的自噬扰动也被观察到-并且与适应性和适应不良的应激反应有关。最近的研究结果表明，各种形式的选择性自噬平行运作，以管理不同的分解代谢“货物”类型，包括线粒体，大蛋白质，糖原和脂质储存。在这篇综述中，考虑了与心脏益处或损害相关的自噬诱导的具体情况。用于测量自噬的各种静态和动态方法的批评和当前的自噬调节的理解在心脏中的矛盾突出。展望未来的药物干预，以实现自噬过程的治疗操作。
Autophagy is a ubiquitous cellular catabolic process responsive to energy stress status. Research over the last decade has revealed that cardiomyocyte autophagy is a prominent homeostatic pathway, important in adaptation to altered myocardial metabolic demand. The cellular machinery of autophagy involves targeted direction of macromolecules and organelles for lysosomal degradation. Autophagy activation has been identified as cardio-protective in some settings (i.e. ischemia and ischemic preconditioning). In other situations chronically elevated levels of autophagy have been linked with cardiopathology (i.e. sustained pressure overload and failure). Autophagy perturbation in diabetic cardiomyopathy is also observed – and has been associated with both adaptive and maladaptive stress responses. Recent findings indicate that various forms of selective autophagy operate in parallel to manage different catabolic ‘cargo’ types including mitochondria, large proteins, glycogen and lipid stores. In this Review, specific circumstances of autophagy induction associated with cardiac benefit or detriment are considered. The various static and dynamic approaches used for measurement of autophagy are critiqued and current inconsistencies in the understanding of autophagy regulation in the heart are highlighted. The future prospects for pharmacological intervention to achieve therapeutic manipulation of autophagic processes are canvassed.
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DOI：
10.18632/aging.100881
发表时间：
2016-02
期刊：
Aging
影响因子：
--
作者：
Chiao YA;Kolwicz SC;Basisty N;Gagnidze A;Zhang J;Gu H;Djukovic D;Beyer RP;Raftery D;MacCoss M;Tian R;Rabinovitch PS
通讯作者：
Rabinovitch PS
DOI：
10.1016/j.bbadis.2010.07.003
发表时间：
2011-01-01
影响因子：
6.2
作者：
Aranguiz-Urroz, Pablo;Canales, Jimena;Diaz-Araya, Guillermo
通讯作者：
Diaz-Araya, Guillermo
DOI：
10.1007/bf02890221
发表时间：
1987-01-01
期刊：
VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY
影响因子：
--
作者：
BAHRO, M;DAMMRICH, J;PFEIFER, U
通讯作者：
PFEIFER, U
影响因子：
9.5
作者：
Ceylan-Isik AF;Dong M;Zhang Y;Dong F;Turdi S;Nair S;Yanagisawa M;Ren J
通讯作者：
Ren J
影响因子：
10.8
作者：
Brennan, Jonathan P.;Southworth, Richard;Shattock, Michael J.
通讯作者：
Shattock, Michael J.