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Elucidating ferroptosis mechanisms in heart failure through transcriptomics, single-cell sequencing, and experimental
Kaiyuan Li1, Peng Liu2, Lingyu Han3
1Graduate School of Dalian Medical University, Dalian Medical University, Dalian, Liaoning 116000, PR China; Department of Cardiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu 225300, PR China.
This study identifies key ferroptosis-related genes (DFRGs) involved in heart failure (HF), revealing potential diagnostic markers and therapeutic targets. Differential expression of SLC39A14 and QSOX1 offers new insights into HF pathophysiology.
Area of Science:
- Biomedical research
- Molecular biology
- Cardiovascular science
Background:
- Mechanisms of ferroptosis in heart failure (HF) are not fully understood.
- Ferroptosis plays a role in the pathophysiology of HF.
Purpose of the Study:
- Identify differentially expressed ferroptosis-related genes (DFRGs) in heart failure.
- Validate key DFRGs as diagnostic biomarkers for HF.
- Explore potential therapeutic targets for HF based on DFRGs.
Main Methods:
- Analyzed Gene Expression Omnibus (GEO) heart failure dataset.
- Utilized LASSO regression and SVM-RFE for DFRG selection.
- Validated DFRGs using single-cell sequencing, cell, and mouse models.
Main Results:
- Identified 127 DFRGs (83 downregulated, 44 upregulated).
- Seven key DFRGs (PTGS2, BECN1, SLC39A14, QSOX1, MLST8, TMSB4X, KDM4A) showed high diagnostic accuracy (AUC 0.988).
- SLC39A14 and QSOX1 showed differential expression in validation models.
Conclusions:
- Novel insights into ferroptosis in heart failure.
- Identified DFRGs, particularly SLC39A14 and QSOX1, as potential contributors to HF pathophysiology.
- Findings support the development of targeted therapies for HF.
