{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:46:03Z","timestamp":1771461963490,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Iron deficiency is a common disorder in patients with heart failure and is related with adverse outcomes and poor quality of life. Previous experimental studies have shown biological connections between iron homeostasis, mitochondrial metabolism, and myocardial function. However, the mechanisms involved in this crosstalk are yet to be unfolded. Methods: The present research attempts to investigate the intrinsic biological mechanisms between heart failure and iron deficiency and to identify potential prognostic biomarkers by determining the gene expression pattern in the blood of heart failure patients, using whole transcriptome and targeted TaqMan\u00ae low-density array analyses. Results: We performed a stepwise cross-sectional longitudinal study in a cohort of chronic heart failure patients with and without systemic iron deficiency. First, the full transcriptome was performed in a nested case-control exploratory cohort of 7 paired patients and underscored 1128 differentially expressed transcripts according to iron status (cohort1#). Later, we analyzed the messenger RNA levels of 22 genes selected by their statistical significance and pathophysiological relevance, in a validation cohort of 71 patients (cohort 2#). Patients with systemic iron deficiency presented lower mRNA levels of mitochondrial ferritin, sirtuin-7, small integral membrane protein 20, adrenomedullin and endothelin converting enzyme-1. An intermediate mitochondrial ferritin gene expression and an intermediate or low sirtuin7 and small integral membrane protein 20 mRNA levels were associated with an increased risk of all-cause mortality and heart failure admission ((HR 2.40, 95% CI 1.04\u20135.50, p-value = 0.039), (HR 5.49, 95% CI 1.78\u201316.92, p-value = 0.003), (HR 9.51, 95% CI 2.69\u201333.53, p-value &lt; 0.001), respectively). Conclusions: Patients with chronic heart failure present different patterns of blood gene expression depending on systemic iron status that affect pivotal genes involved in iron regulation, mitochondrial metabolism, endothelial function and cardiovascular physiology, and correlate with adverse clinical outcomes.<\/jats:p>","DOI":"10.3390\/jcm10214937","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"4937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Blood Differential Gene Expression in Patients with Chronic Heart Failure and Systemic Iron Deficiency: Pathways Involved in Pathophysiology and Impact on Clinical Outcomes"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3734-4777","authenticated-orcid":false,"given":"Carles","family":"D\u00edez-L\u00f3pez","sequence":"first","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Advanced Heart Failure and Heart Transplant Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Clinical Sciences, School of Medicine, University of Barcelona, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Tajes Ordu\u00f1a","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Enjuanes Grau","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-8597","authenticated-orcid":false,"given":"Pedro","family":"Moliner Borja","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Gonz\u00e1lez-Costello","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Advanced Heart Failure and Heart Transplant Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Clinical Sciences, School of Medicine, University of Barcelona, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Garc\u00eda-Romero","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Advanced Heart Failure and Heart Transplant Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Francesch Manzano","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4858-9566","authenticated-orcid":false,"given":"Sergi","family":"Yun Viladomat","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Internal Medicine, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Jim\u00e9nez-Marrero","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Clinical Sciences, School of Medicine, University of Barcelona, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul","family":"Ramos-Polo","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria del Mar","family":"Ras Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Internal Medicine, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-720X","authenticated-orcid":false,"given":"Josep","family":"Com\u00edn-Colet","sequence":"additional","affiliation":[{"name":"Bio-Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Unit, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Clinical Sciences, School of Medicine, University of Barcelona, 08907 Barcelona, Spain"},{"name":"Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bozkurt, B., Coats, A.J., Tsutsui, H., Abdelhamid, M., Adamopoulos, S., Albert, N., Anker, S.D., Atherton, J., B\u00f6hm, M., and Butler, J. 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