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Updated: Jun 7, 2025
Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Unveiling the Molecular Links Between Atrial Fibrillation and Atherosclerosis: Insights into Shared Pathogenesis and
Bowen Xu1,2, Hongye Li1,2, Hongping Chen3
1Qingdao Medical College of Qingdao University, Qingdao, Shandong, 266000, People's Republic of China.
Insights
This study identifies NUPR1 as a key ferroptosis gene involved in the development of atrial fibrillation and atherosclerosis. Understanding these ferroptosis mechanisms offers new therapeutic targets for these common cardiovascular diseases.
Area of Science:
- Cardiovascular Research
- Cell Death Mechanisms
- Biomarker Discovery
Background:
- Atherosclerosis (AS) and atrial fibrillation (AF) are prevalent cardiovascular conditions sharing risk factors like aging, diabetes, obesity, and hypertension.
- Ferroptosis, a distinct form of cell death, is implicated in cardiac disease pathogenesis, highlighting its potential role in AS and AF.
Purpose of the Study:
- To investigate ferroptosis biomarkers associated with atrial fibrillation (AF) and atherosclerosis (AS).
- To elucidate the underlying biological mechanisms of ferroptosis in the context of AF and AS.
Main Methods:
- Analysis of gene expression datasets from the GEO database to identify differentially expressed genes (DEGs) and ferroptosis-related genes (FDGs).
- Functional enrichment analysis (GO, KEGG), network construction, transcription factor prediction, and biomarker identification using LASSO and SVM-RFE algorithms.
- Immune infiltration analysis and cellular experiments, including Western blotting (WB), were performed.
Main Results:
- Identified 1627 DEGs in AF and 571 DEGs in AS, with 128 common DEGs. Discovered 47 common FDGs between AF and AS.
- Functional enrichment revealed associations with leukocyte immunity. Fifteen key genes were identified, with NUPR1 showing high expression in disease models and association with altered immune environments.
- NUPR1 and ITGAM expression differences were verified. Seven transcription factors were predicted to be differentially expressed, and diagnostic models demonstrated good efficacy.
Conclusions:
- The ferroptosis gene NUPR1 plays a significant role in the pathogenesis of both atrial fibrillation and atherosclerosis.
- This study provides critical insights into the molecular mechanisms linking ferroptosis to these cardiovascular diseases.
- Findings suggest NUPR1 as a potential therapeutic target for developing novel treatment strategies for AF and AS.
Objective:
Atherosclerosis(AS) is a vascular disease characterized by the development of plaque in the arteries, and atrial fibrillation (AF) is a common heart arrhythmia. These two conditions share several risk factors in common, such as aging, diabetes, obesity, and hypertension. Ferroptosis is a new mode of non-apoptotic cell death that plays a key role in cardiomyocyte death and has been associated with a variety of cardiac diseases. This study aimed to investigate the ferroptosis biomarkers and underlying biological mechanisms associated with AF and AS.
Materials And Methods:
The gene expression dataset was obtained from GEO database, differentially expressed genes (DEGs) and ferroptosis expressed genes (FDGs) were obtained by data processing and screening, and then functional enrichment, network construction, transcription factor prediction, identification of biomarkers by LASSO and SVM - RFE algorithms, and also immune infiltration analyses and cellular experiments were performed.
Results:
In AF and AS, 1627 and 571 DEGs were identified respectively, and 128 were intersected, and 47 common FDGs were also identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs revealed that they were associated with biological processes and pathways such as leukocyte immunity, and FDGs were also involved in specific functions and pathways. Fifteen key genes were identified, CSF1R and ITGAM expression differences were verified, and seven transcription factors were predicted to be differentially expressed. Characterized genes were screened to construct models with good diagnostic efficacy, and immune infiltration showed that NUPR1 was associated with altered immune environments, and WB indicated that NUPR1 was highly expressed in the disease model.
Conclusion:
Our study demonstrates that the ferroptosis gene NUPR1 plays a role in the pathogenesis of atrial fibrillation and atherosclerosis, and also provides valuable insights into their molecular mechanisms, which may contribute to the development of new targets and strategies for the treatment of these diseases.
