Background

Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear.

Objective

To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism.

Methods

Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively.

Results

The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1.

Conclusion

This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.

中文翻译：

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LncRNA A2M-AS1通过调节IL1R2减轻缺氧和复氧引起的心肌细胞损伤

背景

心肌缺血和再灌注损伤（MI / RI）是一个复杂的病理生理过程，可导致严重的心肌损伤。长的非编码RNA alpha-2-macroglobulin反义RNA 1（A2M-AS1）已被发现在心肌梗死中异常表达，但是，其在心肌梗死中的功能和潜在机制仍不清楚。

目的

目的评估A2M-AS1在缺氧/复氧（H / R）诱导的新生儿心肌细胞中的功能作用及其潜在的分子机制。

方法

数据集GSE66360从GEO数据库获得，用于分析A2M-AS1和2型白介素1受体（IL1R2）的RNA表达。对与A2M-AS1共表达的基因进行KEGG途径富集分析。对人类新生儿心肌细胞进行H / R处理以构建体外模型。采用QRT-PCR和Western blot检测mRNA和蛋白水平。分别通过CCK-8和流式细胞术检测心肌细胞的活力和凋亡。

结果

在H / R处理的心肌细胞中，A2M-AS1的表达明显下调。A2M-AS1的过表达可以显着增强H / R损伤的心肌细胞的细胞活力，而敲低A2M-AS1则显示相反的结果。此外，A2M-AS1与IL1R2的表达呈负相关。在经H / R处理的心肌细胞中，IL1R2的过表达减弱了因过表达A2M-AS1引起的促进增殖和抗凋亡的作用，但是，IL1R2的组合消除了由沉默A2M-AS1引起的抗增殖和促凋亡的作用。

结论

这项研究证明了A2M-AS1 / IL1R2轴在患有H / R的心肌细胞中的潜在调节作用，并为MI / RI的保护提供了见识。