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通过整合生物信息学分析鉴定与心肌梗死相关的关键基因和生物学途径。

Identification of Key Genes and Biological Pathways Related to Myocardial Infarction through Integrated Bioinformatics Analysis.

机构信息

Department of Cardiology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Med Sci. 2023 Jan;48(1):35-42. doi: 10.30476/IJMS.2022.92656.2395.

Abstract

BACKGROUND

Coronary heart disease is the leading cause of death worldwide. Myocardial infarction (MI) is a fatal manifestation of coronary heart disease, which can present as sudden death. Although the molecular mechanisms of coronary heart disease are still unknown, global gene expression profiling is regarded as a useful approach for deciphering the pathophysiology of this disease and subsequent diseases. This study used a bioinformatics analysis approach to better understand the molecular mechanisms underlying coronary heart disease.

METHODS

This experimental study was conducted in the department of cardiology, Aja University of Medical Sciences (2021-2022), Tehran, Iran. To identify the key deregulated genes and pathways in coronary heart disease, an integrative approach was used by merging three gene expression datasets, including GSE19339, GSE66360, and GSE29111, into a single matrix. The test was used for the statistical analysis, with a significance level of P<0.05.

RESULTS

The limma package in R was used to identify a total of 133 DEGs, consisting of 124 upregulated and nine downregulated genes. KDM5D, EIF1AY, and CCL20 are among the top upregulated genes. Moreover, the interleukin 17 (IL-17) signaling pathway and four other signaling pathways were identified as the potent underlying pathogenesis of both coronary artery disease (CAD) and MI using a systems biology approach. Accordingly, these findings can provide expression signatures and potential biomarkers in CAD and MI pathophysiology, which can contribute to both diagnosis and therapeutic purposes.

CONCLUSION

Five signaling pathways were introduced in MI and CAD that were primarily involved in inflammation, including the IL-17 signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and rheumatoid arthritis signaling pathway.

摘要

背景

冠心病是全球范围内导致死亡的主要原因。心肌梗死(MI)是冠心病的致命表现形式,可导致猝死。尽管冠心病的分子机制尚不清楚,但全球基因表达谱分析被认为是破译这种疾病及后续疾病病理生理学的有用方法。本研究采用生物信息学分析方法,以更好地理解冠心病的分子机制。

方法

本实验研究在伊朗德黑兰阿扎大学医学科学学院(2021-2022 年)心内科进行。为了确定冠心病中关键失调基因和途径,采用了一种整合方法,将三个基因表达数据集(GSE19339、GSE66360 和 GSE29111)合并到一个单一的矩阵中。采用 t 检验进行统计分析,显著性水平 P<0.05。

结果

R 中的 limma 包用于鉴定总共 133 个差异表达基因,包括 124 个上调基因和 9 个下调基因。KDM5D、EIF1AY 和 CCL20 是上调基因中的前几个。此外,通过系统生物学方法,鉴定出白细胞介素 17(IL-17)信号通路和其他四个信号通路是冠心病和 MI 的潜在发病机制。因此,这些发现可以为冠心病和 MI 病理生理学提供表达特征和潜在的生物标志物,有助于诊断和治疗目的。

结论

介绍了 MI 和 CAD 中涉及炎症的五个主要信号通路,包括 IL-17 信号通路、TNF 信号通路、Toll 样受体信号通路、C 型凝集素受体信号通路和类风湿关节炎信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f821/9843455/10a1a679ea18/IJMS-48-35-g001.jpg

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