Identification of regulator gene and pathway in myocardial ischemia-reperfusion injury: a bioinformatics and biological validation study.

IF 2.7 3区 生物学
Yanqi Liu, Xiaodong Sheng, Zhenghong Zhao, Hongxia Li, Jiahui Lu, Lihuan Xie, Guanqun Zheng, Tingbo Jiang
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引用次数: 0

Abstract

Background: Acute myocardial infarction (AMI) is the primary cause of cardiac mortality worldwide. However, myocardial ischemia-reperfusion injury (MIRI) following reperfusion therapy is common in AMI, causing myocardial damage and affecting the patient's prognosis. Presently, there are no effective treatments available for MIRI.

Methods: We performed a comprehensive bioinformatics analysis using three GEO datasets on differentially expressed genes, including gene ontology (GO), pathway enrichment analyses, and protein-protein interaction (PPI) network analysis. Cytoscape and LASSO methods were employed to identify novel regulator genes for ischemia-reperfusion (I/R). Notably, gene S100A9 was identified as a potential regulator of I/R. Additionally, clinical sample datasets were analyzed to prove the expression and mechanism of S100A9 and its down genes in I/R. The correlation of S100A9 with cardiac events was also examined to enhance the reliability of our results.

Results: We identified 135 differential genes between the peripheral blood of 47 controls and 92 I/R patients. S100A9 was distinguished as a novel regulator gene of I/R with diagnostic potential. RT-qPCR test demonstrated significant upregulation of S100A9 in I/R. We also verified that S100A9 expression strongly correlates with left ventricular ejection fraction (LVEF) and MIRI.

Conclusion: This study confirms that S100A9 is a key regulator of I/R progression and may participate in ischemia-reperfusion injury by upregulating RAGE /NFKB-NLRP3 activation. Elevated S100A9 levels may serve as a marker for identifying high-risk MIRI patients, especially those with coronary artery no-reflow (CNR), who might benefit from targeted therapeutic interventions. Furthermore, Peripheral blood S100A9 in AMI represents a new therapeutic target for preventing MIRI.

心肌缺血再灌注损伤调控基因及其通路的鉴定:生物信息学和生物学验证研究。
背景:急性心肌梗死(AMI)是世界范围内心脏死亡的主要原因。然而,AMI患者在再灌注治疗后出现心肌缺血再灌注损伤(心肌缺血再灌注损伤,MIRI),造成心肌损害,影响患者预后。目前,对MIRI没有有效的治疗方法。方法:利用三个GEO数据集对差异表达基因进行了全面的生物信息学分析,包括基因本体(GO)、途径富集分析和蛋白质-蛋白质相互作用(PPI)网络分析。采用细胞景观和LASSO方法鉴定缺血再灌注(I/R)的新调控基因。值得注意的是,基因S100A9被确定为I/R的潜在调节因子。此外,通过对临床样本数据的分析,证实了S100A9及其下调基因在I/R中的表达及其机制。我们还检验了S100A9与心脏事件的相关性,以提高我们结果的可靠性。结果:我们在47名对照组和92名I/R患者的外周血中鉴定出135个差异基因。S100A9是一种新的I/R调节基因,具有诊断潜力。RT-qPCR检测显示I/R中S100A9表达显著上调。我们还证实了S100A9的表达与左室射血分数(LVEF)和MIRI密切相关。结论:本研究证实S100A9是I/R进展的关键调控因子,并可能通过上调RAGE /NFKB-NLRP3激活参与缺血再灌注损伤。升高的S100A9水平可以作为识别高危MIRI患者的标志,特别是冠状动脉无血流(CNR)患者,他们可能受益于靶向治疗干预。此外,AMI患者外周血S100A9为预防MIRI提供了新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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