Knockout of Eva1a leads to rapid development of heart failure by impairing autophagy.
Knockout of Eva1a leads to rapid development of heart failure by impairing autophagy.
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Eva1a 的敲除通过损害自噬导致心力衰竭的快速发展
DOI：
10.1038/cddis.2017.17
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发表时间：
2017-02-02
影响因子：
9
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Zhang S;Lin X;Li G;Shen X;Niu D;Lu G;Fu X;Chen Y;Cui M;Bai Y
EVA 1A（伊娃-1同源物A）是一种新的溶酶体和内质网相关蛋白，可调节细胞自噬和凋亡。Eva 1a在心肌中表达，但其在心肌细胞中的功能尚未研究。因此，我们产生了可诱导的，心肌细胞特异性Eva 1a基因敲除小鼠，目的是确定Eva 1a在成人心脏心脏重塑中的作用。实验数据显示，成年心脏中Eva 1a的缺失增加了心脏纤维化，促进了心脏肥大，并导致心肌病和死亡。进一步的研究表明，这种效应与Eva 1a基因敲除心脏中自噬受损和凋亡增加有关。此外，Eva 1a的敲除激活了Mtor信号传导和随后的自噬抑制。此外，Eva 1a基因敲除心脏显示肌节结构紊乱，线粒体错位和聚集，导致缺乏ATP生成。总的来说，这些数据表明Eva 1a通过增加自噬来改善心脏功能并抑制心脏肥大和纤维化。总之，我们的研究结果表明，Eva 1a可能在维持心脏稳态中发挥重要作用。
EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death. Further investigation suggested that this effect was associated with impaired autophagy and increased apoptosis in Eva1a knockout hearts. Moreover, knockout of Eva1a activated Mtor signalling and the subsequent inhibition of autophagy. In addition, Eva1a knockout hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation, leading to the lack of ATP generation. Collectively, these data demonstrated that Eva1a improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing autophagy. In conclusion, our results demonstrated that Eva1a may have an important role in maintaining cardiac homeostasis.