{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:26:34Z","timestamp":1784262394536,"version":"3.55.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":419,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["FP7-242209-BIOSTAT-CHF"],"award-info":[{"award-number":["FP7-242209-BIOSTAT-CHF"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"],"award-info":[{"award-number":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Iron 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We studied 881 patients with HF from the BIOSTAT-CHF cohort. ID was defined as a transferrin saturation\u2009&amp;lt;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\u2013sulfur 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\u20133.11, p\u2009&amp;lt;\u20090.001 hazard ratio 1.78, 95% confidence interval 1.53\u20132.07, p\u2009&amp;lt;\u20090.001, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Iron deficiency is associated with the preservation of heme-related processes at the cost of iron\u2013sulfur 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3562","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T21:33:46Z","timestamp":1735248826000},"page":"2313-2324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Transcriptional Profile of Iron Deficiency in Patients with Heart Failure: Heme-Sparing and Reduced Immune Processes"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-9960","authenticated-orcid":false,"given":"Niels","family":"Grote Beverborg","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridha I.S.","family":"Alnuwaysir","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Markousis-Mavrogenis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn F.","family":"Hoes","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Maastricht UMC+ , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haye H.","family":"van der Wal","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.R.","family":"Romaine","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mintu","family":"Nath","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Koekoemoer","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow , Glasgow ,","place":["UK"]},{"name":"National Heart & Lung Institute, Imperial College , London ,","place":["UK"]},{"name":"Cardiology, Ninewells Hospital and Medical School , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"Cardiology, Ninewells Hospital and Medical School , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) of German Heart Center Charit\u00e9 , Berlin ,","place":["Germany"]},{"name":"Berlin Institute of Health Center for Regenerative Therapies (BCRT) , Berlin ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"Stavanger University Hospital, University of Bergen , Stavanger ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili and University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester BHF Centre of Research Excellence and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der 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