The role of the proteasome in heart disease.
The role of the proteasome in heart disease.
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DOI：
10.1016/j.bbagrm.2010.09.001
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发表时间：
2011-02
影响因子：
4.7
通讯作者：
Wang, Xuejun
中科院分区：
文献类型：
--
作者：
Li, Yi-Fan;Wang, Xuejun
关键词：
对心脏中蛋白酶体的病理生理学意义的深入研究直到过去十年才开始，但已经取得了令人振奋的进展，并在这里总结为两个方面。首先，不断有强有力的证据支持一种新的假说，即蛋白酶体功能不全是心脏病大亚群中的一种常见病理现象，损害了心肌细胞中的蛋白质质量控制，从而成为促进心脏病亚群发展为充血性心力衰竭的主要致病因素。这一前沿体现在对泛素-蛋白酶体系统(UPS)在心脏蛋白病中的研究，这些研究利用了表达UPS蛋白分解功能的荧光报告的转基因小鼠模型。其次，对蛋白酶体的药理抑制作为一种潜在的治疗策略已被实验探索，以干预某些形式的心脏病，如压力超负荷心肌肥厚、病毒性心肌炎和心肌缺血性损伤。不仅在这两条战线之间，而且在每一条战线内部，许多不一致和争议仍有待解释和澄清。目前的争论可能反映了心脏蛋白酶体在组成、组装和调控方面的复杂性，以及心脏病病因和发病机制的复杂性和多样性。蛋白酶体功能改变在各种形式的心脏病发生发展中的确切作用仍有待确定。
Intensive investigations into the pathophysiological significance of the proteasome in the heart did not start until the beginning of the past decade but exciting progresses have been made and are summarized here as two fronts. First, strong evidence continues to emerge to support a novel hypothesis that proteasome functional insufficiency represents a common pathological phenomenon in a large subset of heart disease, compromises protein quality control in heart muscle cells, and thereby acts as a major pathogenic factor promoting the progression of the subset of heart disease to congestive heart failure. This front is represented by the studies on the ubiquitin-proteasome system (UPS) in cardiac proteinopathy, which have taken advantage of a transgenic mouse model expressing a fluorescence reporter for UPS proteolytic function. Second, pharmacological inhibition of the proteasome has been explored experimentally as a potential therapeutic strategy to intervene some forms of heart disease, such as pressure overload cardiac hypertrophy, viral myocarditis, and myocardial ischemic injury. Not only between the two fronts but also within each one, a multitude of inconsistency and controversy remain to be explained and clarified. At present, the controversy perhaps reflects the sophistication of cardiac proteasomes in terms of the composition, assembly, and regulation, as well as the intricacy and diversity of heart disease in terms of its etiology and pathogenesis. A definitive role of altered proteasome function in the development of various forms of heart disease remains to be established.
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影响因子：
20.1
作者：
Divald, Andras;Kivity, Shaye;Powell, Saul R.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1152/ajpheart.2001.281.6.h2612
发表时间：
2001-12-01
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10.8
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影响因子：
4.3
作者：
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