Zhichao Wu, Liang Du, Xunfu Zhang, Chengyu Jin, Jinshan Ma
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引用次数: 0
Abstract
Background: Ischemic cardiomyopathy (ICM), which arises from obstructive coronary artery diseases, is a leading cause of heart failure. Aging is a major risk factor for cardiovascular diseases, yet its connection to ICM remains unclear. This study aimed to investigate the role of aging-related gene expression in the context of ICM.
Methods: Human microarray data (GSE116250) were retrieved from the GEO database and aging-related differentially expressed genes (ARDEGs) were identified using the Aging Atlas database. Functional enrichment and protein-protein interaction (PPI) network analyses were performed to elucidate the functions and interactions of these ARDEGs, leading to the identification of hub genes. The immune infiltration landscape in ICM was further characterized. Subsequently, integrated regulatory networks involving the hub genes were constructed through microRNA-mRNA-transcription factor interaction and GeneMANIA analyses, while their biological functions were inferred via gene set enrichment analysis (GSEA). The predictive value of the hub genes was validated using receiver operating characteristic (ROC) analysis based on both the identification dataset (GSE116250) and an independent validation cohort (GSE1145) Finally,the expression patterns of these genes were verified by RT-qPCR on mouse disease model.
Results: A total of 50 ARDEGs (42 upregulated and 8 downregulated) were identified,which are primarily involved in the response to inflammation. Ten types of immune cells showed significant alterations in the ICM heart tissues. Among these cells, CD56dim NK cells exhibited extensive and significant correlations with other immune cells. JUN was identified as a key transcription factor regulating the top five hub ARDEGs: TNF, PTGS2, IL6, IL1B, and CXCL8. ROC analysis demonstrated that TNF, CXCL8, and IL6 serve as potential biomarkers for ICM, and the combination of the three markers further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregulation of these hub inflammatory ARDEGs in mouse heart tissues.
Conclusion: Aging-related genes play a significant role in ICM and targeting these genes may pave the way for ICM diagnostic and therapeutic strategies.
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Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers?
At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.
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