探索线粒体自噬在缺血性心肌病中的潜在调控机制。
Exploring the Potential Regulatory Mechanisms of Mitophagy in Ischemic Cardiomyopathy.
作者信息
Li Zhaobin, Kong Jiajie, Xi Shuqiang, Jin Zeyue, Yang Fan, Zhu Zhe, Liu Lei
机构信息
Department of Cardiac Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, People's Republic of China.
出版信息
Int J Gen Med. 2025 Jun 5;18:2881-2899. doi: 10.2147/IJGM.S519388. eCollection 2025.
PURPOSE
Ischemic cardiomyopathy (ICM) was a clinical syndrome. Long - term myocardial blood supply insufficiency, caused by coronary atherosclerotic plaque, led to myocardial nutritional disorders and atrophy. After large - scale myocardial infarction, fibrous tissue hyperplasia impaired cardiac systolic and/or diastolic functions, causing heart failure and arrhythmia. Study shows that dysregulated mitophagy can lead to cardiomyocyte death and cardiomyopathy. However, it is still uncertain how mitophagy related genes (MRGs) may affect the diagnosis of ICM.
PATIENTS AND METHODS
Data were obtained from public databases. Subsequently, mitochondria autophagy score-related genes (MSRGs) were obtained through Weighted Gene Co-expression Network Analysis (WGCNA). Then, an intersection was taken between MSRGs and the differentially expressed genes (DEGs) obtained from the differential expression analysis to obtain DE-MSRGs. Then, biomarkers were identified through machine learning algorithms and Receiver Operating Characteristic curve (ROC) analysis. Next, analyses of immune infiltration, molecular regulatory network, and drug prediction were carried out. Finally, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) was performed on the biomarkers. It provides a certain theoretical basis for the research on the mechanism of the occurrence and development of ICM.
RESULTS
In total, 99 DE-MSRGs between ICM and control groups were gained. The four biomarkers (PPDPF, DPEP2, LTBP1, SOCS2) were acquired, and all biomarkers had good diagnostic efficacy for ICM. The content of 3 immune cells between ICM and control groups was significantly different, namely T cells, CD8+ T cells, and neutrophil, and all biomarkers were considerably positively correlated with T cells. The ceRNA network contained 4 mRNAs, 14 miRNAs, and 12 lncRNAs, and TF-mRNA network contained 32 nodes and 38 edges. Finally, 45 drugs targeting the biomarkers were predicted, such as Salmeterol, Histamine, Rotavirus vaccine, etc. Importantly, this all 4 biomarkers were higher in ICM samples in RT-qPCR analysis.
CONCLUSION
Our findings provided four mitophagy related biomarkers (PPDPF, DPEP2, LTBP1, and SOCS2) for diagnosis of ICM, providing a scientific reference for further studies of ICM.
目的
缺血性心肌病(ICM)是一种临床综合征。冠状动脉粥样硬化斑块导致长期心肌供血不足,进而引起心肌营养障碍和萎缩。大面积心肌梗死后,纤维组织增生损害心脏收缩和/或舒张功能,导致心力衰竭和心律失常。研究表明,线粒体自噬失调可导致心肌细胞死亡和心肌病。然而,线粒体自噬相关基因(MRGs)如何影响ICM的诊断仍不确定。
患者和方法
数据来自公共数据库。随后,通过加权基因共表达网络分析(WGCNA)获得线粒体自噬评分相关基因(MSRGs)。然后,将MSRGs与差异表达分析中获得的差异表达基因(DEGs)取交集,以获得DE-MSRGs。接着,通过机器学习算法和受试者工作特征曲线(ROC)分析鉴定生物标志物。随后,进行免疫浸润、分子调控网络和药物预测分析。最后,对生物标志物进行逆转录定量聚合酶链反应(RT-qPCR)。这为ICM发生发展机制的研究提供了一定的理论依据。
结果
共获得ICM组与对照组之间的99个DE-MSRGs。获得了四个生物标志物(PPDPF、DPEP2、LTBP1、SOCS2),所有生物标志物对ICM均具有良好的诊断效能。ICM组与对照组之间3种免疫细胞的含量存在显著差异,即T细胞、CD8+T细胞和中性粒细胞,且所有生物标志物与T细胞均呈显著正相关。ceRNA网络包含4个mRNA、14个miRNA和12个lncRNA,TF-mRNA网络包含32个节点和38条边。最后,预测了45种靶向生物标志物的药物,如沙美特罗、组胺、轮状病毒疫苗等。重要的是,在RT-qPCR分析中,这4种生物标志物在ICM样本中的表达均较高。
结论
我们的研究结果提供了四种用于诊断ICM的线粒体自噬相关生物标志物(PPDPF、DPEP2、LTBP1和SOCS2),为ICM的进一步研究提供了科学参考。