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Updated: May 26, 2025
Isolation and Identification of Extravascular Immune Cells of the Heart
Published on: August 23, 2018
Identification of Necroptosis and Immune Infiltration in Heart Failure Through Bioinformatics Analysis
Yuanting Zhu1, Qiang Zhang2, Yanbo Wang1
1Department of Cardiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People's Republic of China.
Insights
Necroptosis and immune infiltration contribute to heart failure (HF). This study identifies key genes and immune cells involved, offering new therapeutic insights for cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Death Mechanisms
Background:
- Heart failure (HF) is a major cause of death, with necroptosis and immune infiltration implicated.
- The precise mechanisms linking necroptosis and immune cells to HF pathogenesis are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which necroptosis and immune infiltration promote HF.
- To identify potential therapeutic targets for HF management.
Main Methods:
- Analysis of the GSE21610 dataset to identify necroptosis-related differentially expressed genes (NRDEGs) in HF.
- Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network construction.
- Immune infiltration analysis using the CIBERSORT algorithm and validation in animal models.
Main Results:
- 14 NRDEGs were identified in HF, with EGFR, TXN, FASLG, MAPK14, and CASP8 as key hub genes.
- Th1/Th2 cell differentiation, TGF-beta, Renin, and Wnt signaling pathways were associated with HF.
- M2 macrophages, memory B cells, monocytes, Tregs, Tfh cells, and Tgd cells were implicated in HF development, with correlations between hub NRDEGs and immune cells.
Conclusions:
- Necroptosis and immune infiltration are significantly associated with HF development.
- Hub genes like EGFR and FASLG are upregulated, while TXN is downregulated in HF, correlating with immune cell infiltration.
- Findings provide insights for novel therapeutic strategies in HF management.
Purpose:
Heart failure (HF) remains a leading cause of mortality and morbidity in cardiovascular disease. Research has shown that necroptosis contributes to HF, and immune infiltration has been reported to be implicated in HF. However, the specific mechanisms by which necroptosis and immune infiltration promote HF remain poorly understood. This study aims to elucidate these mechanisms, thereby providing new insights for future therapeutic strategies.
Methods And Results:
In the GSE21610 dataset, there were 1848 differentially expressed genes (DEGs), 14 of which related to necroptosis (NRDEGs) in HF. Gene Set Enrichment Analysis (GSEA) indicated that Th1 and Th2 cell differentiation, TGF-beta signaling, Renin secretion, and Wnt signaling pathways may be closely associated with HF. The NRDEGs may play a role in responding to mechanical stimuli, membrane rafts, cytokine receptor binding, or the necroptosis signaling pathway. The protein-protein interaction (PPI) network identified EGFR, TXN, FASLG, MAPK14, and CASP8 as hub NRDEGs. Furthermore, immune infiltration analysis of CIBERSORT algorithm suggested that M2 macrophages, memory B cells, monocytes, regulatory T cells (Tregs), follicular helper T cells, and gamma delta T cells may participate in the development of HF. The hub NRDEGs, including EGFR, FASLG, and TXN, exhibited significant correlations with various immune cell types. Finally, animal models confirmed that in the HF group, EGFR and FASLG were up-regulated, while TXN was down-regulated.
Conclusion:
The present findings demonstrate that necroptosis and immune infiltration are associated with the development of HF. This study provides valuable insights and recommendations for the clinical management of HF.
