Redd1 protects against post-infarction cardiac dysfunction by targeting apoptosis and autophagy
Redd1 protects against post-infarction cardiac dysfunction by targeting apoptosis and autophagy
复制标题
Redd1 通过靶向细胞凋亡和自噬来预防梗死后心脏功能障碍。
DOI：
10.3892/ijmm.2019.4366
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发表时间：
2019-12-01
影响因子：
5.4
通讯作者：
Liu, Lihua
中科院分区：
文献类型：
--
作者：
Huang, Pianpian;Fu, Jun;Liu, Lihua
梗死后重构伴随着雷帕霉素（mTOR）信号转导的哺乳动物靶点的扰动并受其影响。据报道，在发育和DNA损伤反应中受调节的1（Redd 1）参与DNA修复和调节mTOR活性。然而，人们对Redd 1在心脏中的作用知之甚少。本研究探讨了Redd 1过表达对心肌梗死（MI）后心力衰竭慢性期的潜在作用，并确定了Redd 1作用的潜在机制。Redd 1在接受MI手术的小鼠心脏中下调。为了确定Redd 1在MI过程中的作用，使用腺相关病毒9介导的Redd 1过表达来提高心肌细胞中Redd 1的含量。Redd 1过表达改善了左心室功能障碍，降低了扩张指数。此外，Redd 1过表达导致心肌细胞凋亡抑制和自噬改善。此外，研究显示Redd 1过表达可抑制mTOR及其下游效应物P70/S6激酶和4 EBP 1的磷酸化。总之，这项研究表明，Redd 1过表达通过减少细胞凋亡和增强自噬通过mTOR信号通路保护心肌梗死后心力衰竭的发展和持续。本研究清楚地表明，Redd 1是MI后心力衰竭发展的治疗靶点。
Post-infarction remodeling is accompanied and influenced by perturbations in the mammalian target of rapamycin (mTOR) signaling. Regulated in development and DNA damage response-1 (Redd1) has been reported to be involved in DNA repair and modulation of mTOR activity. However, little is known about the role of Redd1 in the heart. In the present study the potential contribution of Redd1 overex-pression to the chronic phase of heart failure after myocardial infarction (MI) was explored and the mechanisms underlying Redd1 actions were determined. Redd1 was downregulated in the mouse heart subjected to MI surgery. To determine the role of Redd1 in the process of MI, adeno-associated virus 9 mediated overexpression of Redd1 was used to enhance Redd1 content in cardiomyocytes. Redd1 overexpression improved left ventricular dysfunction and reduced the expansion index. Additionally, Redd1 overexpression resulted in suppressed myocardial apoptosis and improved autophagy. Furthermore, the studies revealed that Redd1 overexpression could inhibit the phosphorylation of mTOR and its downstream effectors P70/S6 kinase and 4EBP1. In conclusion, this study demonstrated that Redd1 overexpression protects against the development and persistence of heart failure post MI by reducing apoptosis and enhancing autophagy via the mTOR signaling pathway. The present study clearly demonstrated that Redd1 is a therapeutic target in the development of heart failure after MI.