Unveiling Key Biomarkers and Mechanisms in Septic Cardiomyopathy: A Comprehensive Transcriptome Analysis

作者：Dandan Zhao, Jinqiang Zhuang, Liping Wang, Lili Wu, Wangjie Xu, Lu Zhao, Hong Jiang, Wei Jin, Congliang Miao · 发表于：Journal of Inflammation Research · 年份：2024 · DOI：10.2147/jir.s486763 · 被引用次数：4 · 研究领域：Cardiac Fibrosis and Remodeling、Ferroptosis and cancer prognosis、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Purpose: Septic cardiomyopathy (SCM) is a significant global public health concern characterized by substantial morbidity and mortality, which has not been improved for decades due to lack of early diagnosis and effective therapies. This study aimed to identify hub biomarkers in SCM and explore their potential mechanisms. Methods: We utilized the GSE53007 and GSE207363 datasets for transcriptome analysis of normal and SCM mice. Hub biomarkers were identified through a protein-protein interaction (PPI) network and validated using LPS-treated C57/BL6 mice. Functional enrichment analysis was performed to uncover relevant signaling pathways, while single-cell RNA sequencing was used to examine key genes and regulatory mechanisms associated with SCM. Results: A total of 374 differentially expressed genes (DEGs) were identified, with 268 genes up-regulated and 106 genes down-regulated. Functional enrichment highlighted chemokine activity and receptor binding, with KEGG pathways revealing significant involvement of the TNF and IL-7 signaling pathways. Deterioration of cardiac function, elevated inflammatory markers such as IL-1β, IL-6, and increased cardiac injury biomarkers such as cTnI indicated the successful establishment of our SCM model. Subsequently, qPCR was conducted to validate the expression of the top 10 genes, through which we identified Cd40, Tlr2, Cxcl10, Ccl5, Cxcl1, Cd14, Gbp2, Ifit2, and Vegfa as key biomarkers. Single-cell sequencing indicated increased neutrophil...