Diastolic dysfunction and cardiac troponin I decrease in aging hearts.
Diastolic dysfunction and cardiac troponin I decrease in aging hearts.
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DOI：
10.1016/j.abb.2016.05.008
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发表时间：
2016-08-01
影响因子：
3.9
通讯作者：
Tian J
中科院分区：
文献类型：
--
作者：
Pan B;Xu ZW;Xu Y;Liu LJ;Zhu J;Wang X;Nan C;Zhang Z;Shen W;Huang XP;Tian J
心肌肌钙蛋白I（cTnI）在舒张功能的调节中起关键作用，并且其低表达可能导致心脏舒张功能障碍，这是老年人中最常见的心血管疾病形式。在这项研究中，在不同年龄的小鼠中测定cTnI表达水平，并测量和比较年轻成年小鼠（3和10个月）和老年小鼠（18个月）的心脏功能。数据表明，cTnI水平在年轻成人心脏（3个月）中达到峰值，但在老年心脏（18个月）中下降。此外，通过P-V环和超声心动图测量，老年心脏显示出显著的舒张功能障碍。为了进一步确定衰老心脏中cTnI降低的机制，我们检测了cTnI基因的DNA甲基化和组蛋白乙酰化修饰。我们发现cTnI基因启动子区附近的组蛋白乙酰化在不同年龄心肌cTnI表达的调节中起重要作用。我们的研究表明，表观遗传修饰引起的cTnI表达下降是导致老年心脏cTnI水平降低和舒张功能障碍的可能原因之一。
Cardiac tropnoin I (cTnI) plays a critical role in the regulation of diastolic function, and its low expression may result in cardiac diastolic dysfunction, which is the most common form of cardiovascular disorders in older adults. In this study, cTnI expression levels were determined in mice at various ages and cardiac function was measured and compared between young adult mice (3 and 10 months) and older mice (18 months). The data indicated that the cTnI levels reached a peak high in young adult hearts (3 months), but decreased in older hearts (18 months). Furthermore, the older hearts showed a significant diastolic dysfunction observed by P–V loop and echocardiography measurements. To further define the mechanism underlying the cTnI decrease in aging hearts, we tested DNA methylation and histone acetylation modifications of cTnI gene. We found that acetylation of histone near the promoter region of cTnI gene played an important role in regulation of cTnI expression in the heart at different ages. Our study indicates that epigenetic modification caused cTnI expression decrease is one of the possible causes that result in a reduced cTnI level and diastolic dysfunction in the older hearts.