Evidence map›Paper›PMID 40977740›Full record

ArticleFrontiers in immunology2025

Myeloid-specific S100A8/A9 deficiency attenuates atrial fibrillation through prevention of TLR4/NF-kB-mediated immune cell recruitment and inflammation.

Qing Wang, Hua Shen, Jing Wang, Guifang Wang, Yufeng Zhang

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Qing Wang *Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Hua Shen *Department of Cardiovascular Surgery, Chinese PLA General Hospital, Beijing, China.
Jing Wang *Department of Cardiothoracic Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Guifang WangDepartment of Cardiology, Xinxiang City No.1 People's Hospital, Xinxiang, Henan, China.
Yufeng ZhangDepartment of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia, frequently associated with inflammation and atrial remodeling. S100A8/A9, a calcium-binding protein complex enriched in myeloid cells, has been implicated in cardiovascular inflammation, yet its role in AF remains unexplored. This study aims to investigate the mechanistic contribution of myeloid-derived S100A8/A9 to AF pathogenesis and assess its therapeutic potential through targeted genetic deletion. Methods: Transcriptomic and single-cell RNA sequencing data from AF patients were analyzed to identify differentially expressed genes (DEGs) and immune cell signatures. S100A8/A9 emerged as top hub genes. Monocyte/macrophage-specific S100A9 conditional knockout (CKO) mice were subjected to Ach-CaCl Results: S100A8/A9 expression was significantly elevated in atrial tissues and myeloid cell clusters of AF patients. S100A9 CKO mice exhibited reduced AF inducibility and duration, accompanied by attenuation of atrial fibrosis, inflammatory cytokine production, and monocyte infiltration. Mechanistically, S100A9 deletion suppressed activation of the TLR4/IRAK1/TRAF6/NF-κB pathway. These effects were reversed by pharmacologic NF-κB reactivation with HY-18739, confirming the centrality of this pathway. Conclusion: Myeloid-derived S100A8/A9 amplifies AF by promoting monocyte recruitment and inflammation via the TLR4/NF-κB axis. Targeting this pathway may offer a promising therapeutic strategy for AF prevention and treatment.

Indexed as

Atrial FibrillationCalgranulin ACalgranulin BMyeloid CellsNF-kappa BToll-Like Receptor 4AnimalsDisease Models, AnimalFemaleHumansInflammationMaleMiceMice, Inbred C57BLMice, KnockoutMonocytesCalgranulin ACalgranulin BNF-kappa BS100a8 protein, mouseS100A9 protein, mouseTlr4 protein, mouseToll-Like Receptor 4atrial fibrillationconditional knockoutinflammationmonocytesS100A8/A9TLR4/NF-κB signaling

Identifiers

PMID40977740
PMCPMC12443547

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.