Mitochondrial proteome remodeling in ischemic heart failure.
Mitochondrial proteome remodeling in ischemic heart failure.
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DOI：
10.1016/j.lfs.2014.02.004
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发表时间：
2014-04-17
期刊：
影响因子：
6.1
通讯作者：
Knowlton, Anne A.
中科院分区：
文献类型：
--
作者：
Liu, Tingting;Chen, Le;Kim, Eunjung;Tran, Diana;Phinney, Brett S.;Knowlton, Anne A.
关键词：
线粒体功能障碍是心力衰竭时心功能下降的重要组成部分。我们推测，随着缺血性心力衰竭（HF）的进展，线粒体功能和蛋白质组会出现特定的异常。我们在3-4个月大的雄性大鼠中使用高位左前降支（LAD）结扎来产生HF。结扎后9周研究大鼠。电镜下左心室线粒体体积缩小、数量增多、分布异常、嵴缺失。缺血性HF中的线粒体表现出总ATP减少、线粒体呼吸受损以及复合物I活性降低。通过质谱分析LV线粒体蛋白，在500多种总蛋白中鉴定出31种差异表达蛋白（p < 0.05）。在这些蛋白质中，有15种在衰竭的心脏中上调，16种下调。一组复合物I蛋白质显着减少，与复合物I活性的损害一致。缺血性心衰时线粒体功能和蛋白质组发生明显改变。虽然有相似之处，但本研究中报告的TAC压力超负荷诱导的HF和缺血性HF的蛋白质组变化之间的区别表明不同的病理机制。与线粒体功能变化相关的线粒体蛋白表达的特异性变化首次在缺血性HF中被鉴定。
Mitochondrial dysfunction is an important part of the decline in cardiac function in heart failure. We hypothesize that there would be specific abnormalities in mitochondrial function and proteome with the progression of ischemic heart failure (HF). We used a high left anterior descending artery (LAD)ligation in 3–4 month old male rats to generate HF. Rats were studied 9 weeks post ligation. Electron microscopy of left ventricle samples showed, mitochondrial changes including decreased size, increased number, abnormal distribution, and cristae loss. Mitochondria in ischemic HF exhibited decreased total ATP, impaired mitochondrial respiration, as well as reduced complex I activity. Analysis of LV mitochondrial proteins by mass spectrometry was performed, and 31 differentially expressed proteins (p < 0.05) of more than 500 total proteins were identified. Of these proteins, 15 were up-regulated and 16 down-regulated in the failing heart. A set of complex I proteins were significantly decreased, consistent with the impairment of complex I activity. There were distinct changes in mitochondrial function and proteome in ischemic HF. Although there were similarities, the distinction between the reported proteomic changed with TAC pressure overload induced HF and ischemic HF in the current study suggested different pathological mechanisms. Specific changes in mitochondrial protein expression, which correlate with changes in mitochondrial function, have been identified in ischemic HF for the first time.
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影响因子：
10.8
作者：
Chen, Le;Gong, Qizhi;Knowlton, Anne A.
通讯作者：
Knowlton, Anne A.
影响因子：
10.8
作者：
Dai, Dao-Fu;Hsieh, Edward J.;Rabinovitch, Peter S.
通讯作者：
Rabinovitch, Peter S.
DOI：
10.1073/pnas.1002178107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Kuroda, Junya;Ago, Tetsuro;Sadoshima, Junichi
通讯作者：
Sadoshima, Junichi
影响因子：
14.8
作者：
Frezza, Christian;Cipolat, Sara;Scorrano, Luca
通讯作者：
Scorrano, Luca
影响因子：
37.8
作者：
Ide, T;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A