Long noncoding RNA upregulated in hypothermia treated cardiomyocytes protects against myocardial infarction through improving mitochondrial function
Long noncoding RNA upregulated in hypothermia treated cardiomyocytes protects against myocardial infarction through improving mitochondrial function
复制标题
低温处理的心肌细胞中长链非编码RNA上调可通过改善线粒体功能来预防心肌梗死
DOI：
10.1016/j.ijcard.2017.12.097
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Wang, Huishan
中科院分区：
文献类型：
--
作者：
Zhang, Jian;Yu, Liming;Wang, Huishan
背景：心肌梗死（MI）是引起心脏疾病和死亡的最常见原因之一。许多证据表明，作为心肌梗死的辅助治疗，低温治疗对减少梗死面积有更明显的影响。然而，长链非编码rna （lncRNA）在治疗性低温治疗心肌梗死中的作用仍然知之甚少。方法：在本研究中，我们研究了lncRNA-UIHTC（在低温处理的心肌细胞中上调，NONHSAT094064）在缺血心脏组织中的表达。为了研究其功能，采用腺相关病毒载体对心肌梗死大鼠进行过表达。结果：lncRNA-UIHTC在缺血或损伤心肌细胞中表达上调。lncRNA-UIHTC在梗死期过表达可减轻体内心功能障碍。在机制上，lncRNA-UIHTC通过上调PGC1 α来增强线粒体功能。此外，当我们敲除PGC1a时，因过表达UIHTC而增加的线粒体最大耗氧量和ATP水平几乎完全恢复。结论：总之，我们提供了低温通过lncRNA-UIHTC保护心脏免受缺血的新机制。uhtc为心肌梗死提供了一个新的潜在治疗靶点，同时防止了低温症的并发症。(C) 2018 Elsevier B.V.版权所有
Background: Myocardial infarction (MI) is one of the most common causes of cardiac morbidity and mortality. Many evidences suggest that hypothermia have a more pronounced impact as an adjunctive therapy for MI to reduce infarct size. However, the function of long non-coding RNAs (lncRNA) in therapeutic hypothermia for MI remains poorly understood.Methods: In this study, we investigated the expression of lncRNA-UIHTC (upregulated in hypothermia treated cardiomyocytes, NONHSAT094064) in ischemic heart tissues. To investigate its function, overexpression of UIHTC was performed by adeno-associated virus vectors after MI model in rat.Results: lncRNA-UIHTC was upregulated in ischemic or injury cardiomyocytes. Overexpression of lncRNA-UIHTC in peri-infarction attenuated cardiac dysfunction in vivo. Mechanistically, lncRNA-UIHTC enhanced the mitochondrial function via upregulation of PGC1 alpha. Moreover, when we knocked down PGC1a, the mitochondrial maximal oxygen consumption and ATP levels enhanced by overexpression of UIHTC were nearly completely restored.Conclusions: Altogether we have provided a new mechanism whereby hypothermia protected heart against ischemic via lncRNA-UIHTC. The UIHTC provided a new potential therapeutic target for MI but prevented the complications of hypothermia. (C) 2018 Elsevier B.V. All rights reserved.