Evidence map›Paper›PMID 39725571›Full record

ArticleEuropean journal of heart failure2025

The transcriptional profile of iron deficiency in patients with heart failure: Heme-sparing and reduced immune processes.

Niels Grote Beverborg, Ridha I S Alnuwaysir, George Markousis-Mavrogenis, Martijn F Hoes, Haye H van der Wal, Simon P R Romaine, Mintu Nath, Andrea Koekoemoer, John G F Cleland, Chim C Lang and 8 more

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In one paragraph

Article in European journal of heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Iron Deficiency in Heart Failure: Cellular Mechanisms and Therapeutic Implications.Journal of cardiovascular development and disease · 2025
    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

18 authors.

Niels Grote BeverborgDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.ORCID https://orcid.org/0000-0003-4629-9960
Ridha I S AlnuwaysirDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
George Markousis-MavrogenisDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Martijn F HoesClinical Genetics, Maastricht UMC+, Maastricht, The Netherlands.
Haye H van der WalDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Simon P R RomaineDepartment of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Mintu NathDepartment of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Andrea KoekoemoerDepartment of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
John G F ClelandRobertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, UK.
Chim C LangCardiology, Ninewells Hospital and Medical School, Dundee, UK.
Stefan D AnkerDepartment of Cardiology (CVK) of German Heart Center Charité, Berlin, Germany.
Kenneth DicksteinStavanger University Hospital, University of Bergen, Stavanger, Norway.
Marco MetraASST Spedali Civili and University of Brescia, Brescia, Italy.
Leong L NgDepartment of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Dirk J van VeldhuisenDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Adriaan A VoorsDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Peter van der MeerDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

Funding

Horizon 2020 Framework Programme FP7-242209-BIOSTAT-CHF
6 · The paper itself

Abstract

aimsIron deficiency (ID) is highly prevalent in patients with heart failure (HF) and associated with morbidity and poor prognosis, but pathophysiological mechanisms are unknown. We aimed to identify novel biological pathways affected by ID. METHODS AND

resultsWe studied 881 patients with HF from the BIOSTAT-CHF cohort. ID was defined as a transferrin saturation <20%. Transcriptome profiling was performed in whole blood. Identified targets were validated in a human in vitro stem cell-derived cardiomyocyte ID model utilizing deferoxamine as iron chelator. ID was identified in 554 (62.9%) patients, and 89 differentially expressed genes between ID and non-ID were identified, of which 60 were up- and 29 were downregulated. Upregulated genes were overrepresented in pathways of erythrocyte development and homeostasis. Heme biosynthetic processes were confirmed as relatively upregulated in ID, while iron-sulfur cluster assembly was downregulated. Downregulated processes further included natural killer cell and lymphocyte mediated immunity. In agreement with patient data, cardiomyocyte iron depletion significantly induced the expression of two genes (SIAH2 and CLIC4), which could be normalized upon iron supplementation. Both SIAH2 and CLIC4 are associated with increased mortality in patients with HF (hazard ratio 2.40, 95% confidence interval 1.86-3.11, p < 0.001 hazard ratio 1.78, 95% confidence interval 1.53-2.07, p < 0.001, respectively).

conclusionIron deficiency is associated with the preservation of heme-related processes at the cost of iron-sulfur clusters. Immune processes are downregulated, uncovering another high energy demand system affected. SIAH2 and CLIC4 might be modifiable factors in the relation between ID and impaired prognosis.

Indexed as

Anemia, Iron-DeficiencyHeart FailureHemeIron DeficienciesTranscriptomeAgedFemaleGene Expression ProfilingHumansIronMaleMiddle AgedMyocytes, CardiacPrognosisHemeIronHeart failureHemeIron deficiencyIron–sulfurTranscriptome profiling

Identifiers

PMID39725571
PMCPMC12765047

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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.