Evidence map›Paper›PMID 41408106›Full record

ArticleScientific reports2025

Metformin mitigates aortic valve degeneration in an ex vivo three-dimensional tissue model.

Friederike Irmgard Schoettler, Andreas Weber, Vera Schmidt, Sebastian Johannes Bauer, Moritz Benjamin Immohr, Artur Lichtenberg, Payam Akhyari, Mareike Barth

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Friederike Irmgard SchoettlerDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Andreas WeberDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Vera SchmidtDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Sebastian Johannes BauerDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Moritz Benjamin ImmohrDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Artur LichtenbergDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Payam AkhyariDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Payam.Akhyari@uk-essen.de.
Mareike BarthDepartment of Cardiovascular Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Calcific aortic valve disease (CAVD) is a prevalent valvular disorder that lacks effective pharmacological treatments. Metformin, an oral anti-diabetic drug, has been suggested to protect valvular interstitial cells (VICs) from calcification, but its role in preventing organic phosphate-induced degeneration in VICs and aortic valve (AV) leaflets remains unclear. Using an ex vivo three-dimensional tissue model, we induced degeneration with organic phosphate-rich conditions in ovine VICs and AV leaflets. Metformin treatment reduced calcium deposition, as assessed by alizarin red staining (VICs: p < 0.0001; AV leaflets: p < 0.05), and preserved reduced opacity of AV leaflet (p < 0.01). It inhibited early osteogenic differentiation, evidenced by reduced alkaline phosphatase activity (VICs: p < 0.0001; AV leaflets: p < 0.05), and mitigated gene expression of myofibroblastic markers. Furthermore, metformin improved proliferation (VICs: p < 0.0001; AV leaflets: p < 0.05), lowered lactate dehydrogenase levels (VICs: p < 0.01; AV leaflets: p < 0.001), preserved extracellular matrix architecture, and ameliorated extracellular matrix remodeling at gene expression level. AMPK phosphorylation was increased in both VICs (28%, p < 0.001) and AV leaflets (21%, p < 0.05) under pro-degenerative conditions and metformin treatment. In conclusion, metformin protects against organic phosphate-induced degeneration in both VICs and AV leaflets, highlighting its therapeutic potential in CAVD.

Indexed as

Aortic ValveAortic Valve StenosisCalcinosisMetforminAnimalsCell DifferentiationCell ProliferationExtracellular MatrixOsteogenesisSheepMetforminAMPK signalingAortic valve degenerationCalcific aortic valve diseaseMetforminValvular interstitial cells (VIC)

Identifiers

PMID41408106
PMCPMC12715251

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.