Evidence map›Paper›PMID 41077867›Full record

ArticleACR open rheumatology2025

Mapping Drivers of Coronary Endothelial Activation and Endothelial-to-Mesenchymal Transition through Mimicking of Multimediator Inflammation in Kawasaki Disease Context.

Pia Buthe, Marie Carlotta Limburg, Sabrina Fuehner, Julia Kuehn, André Jakob, Isabelle Koné-Paut, Stéphanie Tellier, Alexandre Belot, Linda Rossi-Semerano, Perrine Dusser-Benesty and 7 more

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Article in ACR open rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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

17 authors.

Pia ButheDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
Marie Carlotta LimburgDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
Sabrina FuehnerDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
Julia KuehnDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
André JakobDepartment of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University, Munich, Germany.
Isabelle Koné-PautDivision of Pediatric Rheumatology and CEREMAIA, Bicêtre Hospital, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France.ORCID https://orcid.org/0000-0001-8939-5763
Stéphanie TellierDepartment of Pediatrics, Divisions of Nephrology, Rheumatology and Internal Medicine, University of Toulouse, Toulouse, France.
Alexandre BelotDepartments of Pediatrics, Division of Rheumatology, Dermatology and Nephrology, University of Lyon, Lyon, France.
Linda Rossi-SemeranoDivision of Pediatric Rheumatology and CEREMAIA, Bicêtre Hospital, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France.ORCID https://orcid.org/0000-0002-3724-1460
Perrine Dusser-BenestyDivision of Pediatric Rheumatology and CEREMAIA, Bicêtre Hospital, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France.ORCID https://orcid.org/0000-0001-8118-0848
Isabelle MarieDivision of Pediatric Rheumatology and CEREMAIA, Bicêtre Hospital, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France.
Jana MerfortDepartment of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.
Katja MasjosthusmannDepartment of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.
Claas HinzeDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.ORCID https://orcid.org/0000-0001-9247-4729
Helmut WittkowskiDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
Dirk FoellDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.ORCID https://orcid.org/0000-0002-1946-3916
Christoph KesselDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.ORCID https://orcid.org/0000-0002-0638-2949

Funding

Deutsche Forschungsgemeinschaft FO354/14-1Deutsche Forschungsgemeinschaft KE 2026 1/3Novartis Pharma
6 · The paper itself

Abstract

objectiveKawasaki disease (KD) is an acute systemic vasculitis predominantly affecting coronary arteries of infants and children. We recently identified leucin-rich α-2-glycoprotein 1 (LRG-1) as known transforming growth factor β1 (TGFβ1) signal-modulating molecule, orchestrating endothelial activation and cardiac remodeling, as associated with interleukin-1β (IL-1β) signaling in KD. In the present study, we aimed to assess the role for LRG-1 as part of a multimediator inflammatory environment as a possible direct mediator of human coronary artery endothelial activation.

methodsHuman coronary artery endothelial cells (HCAECs) were treated with a blood inflammatory matrix, with or without targeted inhibition of several inflammatory mediators, including LRG-1, and were analyzed for inflammatory activation or endothelial-to-mesenchymal transition (EndMT) on gene expression level. Proteomic profiling of the inflammatory matrix, treatment-naïve KD (n = 11), or healthy control serum samples (n = 10) was performed by proximity extension assay (n = 184 markers) and Luminex.

resultsProteomic analysis of KD serum samples and the inflammatory matrix revealed elevation of 37 versus 50 inflammatory proteins, respectively, with 19 significantly up-regulated markers shared. The HCAEC culture with the inflammatory matrix resulted in inflammatory endothelial activation, which was most efficiently abrogated by IL-1 receptor type 1 (IL-1R1) inhibition compared to all other tested drugs. Whereas inflammatory endothelial activation can also link to TGFβ-driven EndMT, which was supported by respective signatures in our KD serum proteomics, we observed that in vitro inflammatory matrix-induced EndMT was partly impaired by both IL-1R1 and tumor necrosis factor inhibition compared to other tested drugs.

conclusionsCollectively, our observations in the context of a multimediator inflammatory environment indicate a prominent role of a specific clinically relevant cytokine signaling axis in inflammatory coronary artery endothelial activation and EndMT in the context of KD.

Identifiers

PMID41077867
PMCPMC12516014

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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 OpenQuestion graph.