ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Cardiovascular Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1429465
This article is part of the Research TopicThe Role of Metabolic Syndrome and Disorders in Cardiovascular Disease - Volume IIView all 23 articles
Decoding the Mystery Between Hyperuricemia and Atrial Fibrillation: New Causal Links through Mediating Proteomics
Provisionally accepted
- Bethune First Hospital of Jilin University, Changchun, China
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Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with high incidence and mortality rates. Recent studies have confirmed a close correlation between hyperuricemia and the onset of AF, though the mechanisms remain unclear. Consequently, this study employs Mendelian randomization based on proteomics and mediation analysis to investigate the potential mechanisms by which hyperuricemia induces AF.A two-step mediation MR analysis was conducted to determine whether plasma proteins mediate atrial fibrillation induced by serum urate. The Reactome database was subsequently utilized to analyze the list of significant mediating plasma proteins to identify enriched pathways.Results: Mediation Mendelian randomization analysis suggested that hyperuricemia may promote the development of atrial fibrillation (AF) through 17 plasma proteins, including hepatocyte nuclear factor 4-alpha (HNF4α), identified as key mediators. Subsequent enrichment analysis of these proteins revealed 9 metabolic or signaling pathways potentially involved in this pathological process.Central mediator proteins such as HNF4α appear to drive AF through metabolic and inflammatory pathways.There is a close correlation between hyperuricemia and the onset of atrial fibrillation.
Keywords: Atrial Fibrillation, Hyperuricemia, mediation mendelian randomization, Proteomics, mediation analanalysis
Received: 08 May 2024; Accepted: 30 Apr 2025.
Copyright: © 2025 Zhang, Shi, Qin, Peng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhiguo Zhang, Bethune First Hospital of Jilin University, Changchun, China
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