Liu Yanqi, Sheng Xiaodong, Zhao Zhenghong, Li Hongxia, Lu Jiahui, Xie Lihuan, Zheng Guanqun, Jiang Tingbo
Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Cardiology, The Second People's Hospital of Changshu, Affiliated Changshu Hospital of Nantong University, Changshu, Suzhou, Jiangsu, China.
Hereditas. 2025 Mar 11;162(1):35. doi: 10.1186/s41065-025-00397-5.
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.
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.
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.
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.
急性心肌梗死（AMI）是全球心脏性死亡的主要原因。然而，再灌注治疗后的心肌缺血再灌注损伤（MIRI）在AMI中很常见，会导致心肌损伤并影响患者预后。目前，对于MIRI尚无有效的治疗方法。
我们使用三个基因表达综合数据库（GEO）数据集对差异表达基因进行了全面的生物信息学分析，包括基因本体论（GO）、通路富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。采用Cytoscape和套索（LASSO）方法来识别缺血再灌注（I/R）的新型调节基因。值得注意的是，基因S100A9被确定为I/R的潜在调节因子。此外，对临床样本数据集进行分析，以证实S100A9及其下游基因在I/R中的表达和机制。还检测了S100A9与心脏事件的相关性，以提高我们结果的可靠性。
我们在47名对照者和92名I/R患者的外周血中鉴定出135个差异基因。S100A9被确定为具有诊断潜力的I/R新型调节基因。逆转录-定量聚合酶链反应（RT-qPCR）检测表明I/R中S100A9显著上调。我们还证实S100A9表达与左心室射血分数（LVEF）和MIRI密切相关。
本研究证实S100A9是I/R进展的关键调节因子，可能通过上调晚期糖基化终末产物受体（RAGE）/核因子κB（NFKB）-NOD样受体蛋白3（NLRP3）激活参与缺血再灌注损伤。S100A9水平升高可能作为识别高危MIRI患者的标志物，尤其是那些冠状动脉无复流（CNR）患者，他们可能从靶向治疗干预中获益。此外，AMI患者外周血中的S100A9代表了预防MIRI的新治疗靶点。
