Background

Following the recent discovery that microRNA-134-5p (miR-134-5p) is elevated in the early stages of acute myocardial infarction (AMI), we examined the specific role of miR-134-5p in cardiomyocytes during AMI.

Methods

To study miR-134-5p's role in the context of AMI, we used a combination of in vitro experiments in H₂O₂–treated or hypoxic cardiomyocyte cell cultures as well as in vivo experiments in a murine model of AMI.

Results

H₂O₂- and hypoxia-induced cardiomyocyte injury upregulated miR-134-5p expression. miR-134-5p overexpression increased cardiomyocyte apoptosis, whereas miR-134-5p inhibition reduced cardiomyocyte apoptosis. We discovered that the transcription factor cAMP-responsive element binding protein 1 (Creb1) is a functional target of miR-134-5p responsible for regulating cardiomyocyte apoptosis. In vivo AMI resulted in the upregulation and downregulation of miR-134-5p and Creb1 in the infarct area, respectively. Circulating miR-134-5p levels were also increased at days 1 and 2 post-AMI. Modulation of myocardial miR-124-5p expression by intramyocardial injection of antagomiR-134-5p or agomiR-134-5p significantly affected cardiomyocyte apoptosis, infarct size, and cardiac function in vivo.

Conclusions

miR-134-5p/Creb1 axis dysregulation plays a role in hypoxia- or oxidative stress-induced cardiomyocyte apoptosis as well as AMI. Circulating miR-134-5p may show promise as a biomarker for AMI or post-AMI cardiac dysfunction. Manipulating the miR-134-5p/Creb1 axis through either inhibition of miR-134-5p or overexpression of Creb1 may show promise as a novel therapeutic strategy to attenuate cardiac dysfunction following AMI.

中文翻译：

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miR-134-5p抑制通过Creb1上调减少了梗死诱导的心肌细胞凋亡。

背景

根据最近的发现，在急性心肌梗塞（AMI）的早期阶段，microRNA-134-5p（miR-134-5p）升高了，我们检查了AMI期间miR-134-5p在心肌细胞中的特定作用。

方法

为了研究miR-134-5p在AMI中的作用，我们结合了在H ₂ O ₂处理或缺氧的心肌细胞培养物中的体外实验以及在AMI小鼠模型中的体内实验。

结果

H ₂ O _2-和缺氧诱导的心肌损伤上调了miR-134-5p表达。miR-134-5p过表达增加了心肌细胞的凋亡，而miR-134-5p抑制则减少了心肌细胞的凋亡。我们发现，转录因子cAMP反应元件结合蛋白1（Creb1）是负责调节心肌细胞凋亡的miR-134-5p的功能靶标。体内AMI分别导致梗死区域miR-134-5p和Creb1的上调和下调。AMI后第1天和第2天循环miR-​​134-5p水平也增加。通过心肌内注射antagomiR-134-5p或agomiR-134-5p来调节心肌miR-124-5p表达，可显着影响体内的心肌细胞凋亡，梗塞面积和心脏功能。

结论

miR-134-5p / Creb1轴失调在缺氧或氧化应激诱导的心肌细胞凋亡以及AMI中起作用。循环中的miR-134-5p可能有望成为AMI或A​​MI后心脏功能障碍的生物标志物。通过抑制miR-134-5p或过度表达Creb1来操纵miR-134-5p / Creb1轴可能显示出作为减轻AMI后心脏功能障碍的新型治疗策略的希望。