{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:08:56Z","timestamp":1781284136929,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T00:00:00Z","timestamp":1644019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Cardinal Stefan Wyszy\u0144ski National Institute of Cardiology, Grant No. 3.15\/VII\/18","award":["Grant No. 3.15\/VII\/18"],"award-info":[{"award-number":["Grant No. 3.15\/VII\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In heart failure, iron deficiency is a common comorbid disease that negatively influences exercise tolerance, number of hospitalizations and mortality rate, and this is why iron iv supplementation is recommended. Little is known about the changes in iron-related proteins in the human HF myocardium. The purpose of this study was to assess iron-related proteins in non-failing (NFH) vs. failing (FH) human myocardium. The study group consisted of 58 explanted FHs; control consisted of 31 NFHs unsuitable for transplantation. Myocardial proteins expressions: divalent metal transporter (DMT-1); L-type calcium channel (L-CH); transferrin receptors (TfR-1\/TfR-2); ferritins: heavy (FT-H) or light (FT-L) chain, mitochondrial (FT-MT); ferroportin (FPN), regulatory factors and oxidative stress marker: 4-hydroxynonenal (4-HNE). In FH, the expression in almost all proteins responsible for iron transport: DMT-1, TfR-1, L-CH, except TfR-2, and storage: FT-H\/-L\/-MT were reduced, with no changes in FPN. Moreover, 4-HNE expression (pg\/mg; NFH 10.6 \u00b1 8.4 vs. FH 55.7 \u00b1 33.7; p &lt; 0.0001) in FH was increased. HNE-4 significantly correlated with DMT-1 (r = \u22120.377, p = 0.036), L-CH (r = \u22120.571, p = 0.001), FT-H (r = \u22120.379, p = 0.036), also FPN (r = 0.422, p = 0.018). Reducing iron-gathering proteins and elevated oxidative stress in failing hearts is very unfavorable for myocardiocytes. It should be taken into consideration before treatment with drugs or supplements that elevate free oxygen radicals in the heart.<\/jats:p>","DOI":"10.3390\/jcm11030837","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:38:40Z","timestamp":1644179920000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Expression of Iron Metabolism Proteins in Patients with Chronic Heart Failure"],"prefix":"10.3390","volume":"11","author":[{"given":"Bogna","family":"Koz\u0142owska","sequence":"first","affiliation":[{"name":"Department of Heart Failure and Transplantology, The Cardinal Stefan Wyszy\u0144ski National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Sochanowicz","sequence":"additional","affiliation":[{"name":"Centre of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Kraj","sequence":"additional","affiliation":[{"name":"Department of Oncology, Medical University of Warsaw, 01-163 Warsaw, Poland"},{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, Post\u0119pu 36A, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-5280","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Palusi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, Post\u0119pu 36A, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ko\u0142sut","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery and Transplantology, The Cardinal Stefan Wyszy\u0144ski National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-541X","authenticated-orcid":false,"given":"\u0141ukasz","family":"Szyma\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, Post\u0119pu 36A, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-0680","authenticated-orcid":false,"given":"S\u0142awomir","family":"Lewicki","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, Post\u0119pu 36A, 05-552 Magdalenka, Poland"},{"name":"Faculty of Medical Sciences and Health Sciences, Kazimierz Pulaski University of Technology and Humanities, 26-600 Radom, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witold","family":"\u015amigielski","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, The Cardinal Stefan Wyszy\u0144ski National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Kruszewski","sequence":"additional","affiliation":[{"name":"Centre of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warszawa, Poland"},{"name":"Department of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw","family":"Leszek","sequence":"additional","affiliation":[{"name":"Department of Heart Failure and Transplantology, The Cardinal Stefan Wyszy\u0144ski National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/ehjcvp\/pvu016","article-title":"Iron deficiency in patients with heart failure","volume":"1","author":"Fitzsimons","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-981-13-9589-5_2","article-title":"Cellular iron metabolism and regulation","volume":"1173","author":"Gao","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e008100","DOI":"10.1161\/CIRCHEARTFAILURE.120.008100","article-title":"Randomized placebo-controlled trial of ferric carboxymaltose in heart failure with iron deficiency: Rationale and design","volume":"14","author":"Mentz","year":"2021","journal-title":"Circ. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100871","DOI":"10.1016\/j.ijcha.2021.100871","article-title":"Effect of iron supplementation in patients with heart failure and iron deficiency: A systematic review and meta-analysis","volume":"36","author":"Yamani","year":"2021","journal-title":"IJC Heart Vasc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/S0140-6736(20)32339-4","article-title":"Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: A multicentre, double-blind, randomised, controlled trial","volume":"396","author":"Ponikowski","year":"2020","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18132","DOI":"10.1038\/srep18132","article-title":"Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy","volume":"5","author":"Das","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1097\/01.fjc.0000159659.78675.4a","article-title":"Paradoxical effects of iron chelation on growth of vascular endothelial cells","volume":"45","author":"Hodges","year":"2005","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3728","DOI":"10.3760\/cma.j.issn.0366-6999.20130677","article-title":"inhibitory effect of iron on in vitro proliferation of smooth muscle cells","volume":"126","author":"Wu","year":"2013","journal-title":"Chin. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/jcla.20335","article-title":"Oxidative status in iron-deficiency anemia","volume":"23","author":"Yoo","year":"2009","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e5395","DOI":"10.1097\/MD.0000000000005395","article-title":"Impact of iron deficiency anemia on the function of the immune system in children","volume":"95","author":"Hassan","year":"2016","journal-title":"Medicine"},{"key":"ref_12","first-page":"164","article-title":"Review on iron and its importance for human health","volume":"19","author":"Abbaspour","year":"2014","journal-title":"J. Res. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.molmed.2011.07.004","article-title":"Iron Disorders of genetic origin: A changing world","volume":"17","author":"Brissot","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/joim.13004","article-title":"Iron deficiency anaemia revisited","volume":"287","author":"Cappellini","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCULATIONAHA.118.030099","article-title":"Anemia and iron deficiency in heart failure: Current concepts and emerging therapies","volume":"138","author":"Anand","year":"2018","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ahj.2013.01.017","article-title":"Iron deficiency in chronic heart failure: An international pooled analysis","volume":"165","author":"Klip","year":"2013","journal-title":"Am. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"709872","DOI":"10.3389\/fcvm.2021.709872","article-title":"Iron deficiency: A new target for patients with heart failure","volume":"8","author":"Rizzo","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1001\/jama.2017.5427","article-title":"Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF randomized clinical trial","volume":"317","author":"Lewis","year":"2017","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0162-0134(02)00461-0","article-title":"Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells","volume":"91","author":"Crichton","year":"2002","journal-title":"J. Inorg. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.bbadis.2018.08.030","article-title":"Role of iron metabolism in heart failure: From iron deficiency to iron overload","volume":"1865","author":"Zhang","year":"2019","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.trsl.2010.11.002","article-title":"Interdependence of cardiac iron and calcium in a murine model of iron overload","volume":"157","author":"Brewer","year":"2011","journal-title":"Transl. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1182\/blood-2016-06-721183","article-title":"A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major","volume":"128","author":"Fernandes","year":"2016","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3109\/03630269.2014.987869","article-title":"Cardiomyopathy associated with iron overload: How does iron enter myocytes and what are the implications for pharmacological therapy?","volume":"39","author":"Wijarnpreecha","year":"2015","journal-title":"Hemoglobin"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/109980040200300404","article-title":"Amlodipine decreases iron uptake and oxygen free radical production in the heart of chronically iron overloaded mice","volume":"3","author":"Crowe","year":"2002","journal-title":"Biol. Res. Nurs."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jacc.2011.01.059","article-title":"Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure","volume":"58","author":"Maeder","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ijcard.2011.08.006","article-title":"Myocardial iron homeostasis in advanced chronic heart failure patients","volume":"159","author":"Leszek","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ijcard.2015.01.006","article-title":"Does myocardial iron load determine the severity of heart insufficiency?","volume":"182","author":"Leszek","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_28","first-page":"e6864723","article-title":"Salvia Miltiorrhiza (SM) injection ameliorates iron overload-associated cardiac dysfunction by regulating the expression of DMT1, TfR1, and FP1 in rats","volume":"2021","author":"Zhang","year":"2021","journal-title":"Evid.-Based Complementary Altern. Med."},{"key":"ref_29","first-page":"A15973","article-title":"Abstract 15973: Ebselen, a divalent metal transporter 1 inhibitor, effectively blocks iron entry to human Ipsc-derived cardiomyocytes and prevents iron-overload cardiotoxicity","volume":"140","author":"Rhee","year":"2019","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.celrep.2015.09.023","article-title":"Lethal cardiomyopathy in mice lacking transferrin receptor in the heart","volume":"13","author":"Xu","year":"2015","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13578-021-00605-5","article-title":"Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells","volume":"11","author":"Tajes","year":"2021","journal-title":"Cell Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1073\/pnas.1422373112","article-title":"Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function","volume":"112","author":"Wolna","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fphar.2014.00034","article-title":"The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body","volume":"5","author":"Worthen","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/ejh.13183","article-title":"Ferritin heavy\/light chain (FTH1\/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia","volume":"102","author":"Bertoli","year":"2019","journal-title":"Eur. J. Haematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fphar.2014.00019","article-title":"Mitochondrial ferritin in the regulation of brain iron homeostasis and neurodegenerative diseases","volume":"5","author":"Gao","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1182\/blood.V89.3.1052","article-title":"Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency","volume":"89","author":"Punnonen","year":"1997","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ejhf.701","article-title":"Ferritin levels and risk of heart failure\u2014The atherosclerosis risk in communities study","volume":"19","author":"Silvestre","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1161\/CIRCRESAHA.120.316509","article-title":"Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis","volume":"127","author":"Fang","year":"2020","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/labinvest.2017.111","article-title":"Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology","volume":"98","author":"Vela","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1182\/blood-2017-05-786590","article-title":"Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin","volume":"131","author":"Aschemeyer","year":"2018","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e19804","DOI":"10.7554\/eLife.19804","article-title":"An essential cell-autonomous role for hepcidin in cardiac iron homeostasis","volume":"5","author":"Wolna","year":"2016","journal-title":"eLife"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/eurheartj\/ehs377","article-title":"Iron status in patients with chronic heart failure","volume":"34","author":"Jankowska","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114661","DOI":"10.1016\/j.bcp.2021.114661","article-title":"Dysregulation of iron metabolism in cardiovascular diseases: From iron deficiency to iron overload","volume":"190","author":"Bi","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_44","first-page":"362","article-title":"Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure","volume":"38","author":"Haddad","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"C314","DOI":"10.1152\/ajpcell.00374.2004","article-title":"Expression of constitutively stable hybrid hypoxia-inducible factor-1\u03b1 protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury","volume":"288","author":"Date","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.bbrc.2008.08.152","article-title":"Activation of negative regulators of the hypoxia-inducible factor (HIF) pathway in human end-stage heart failure","volume":"376","author":"Zolk","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nature05602","article-title":"P53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload","volume":"446","author":"Sano","year":"2007","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.bbadis.2015.01.015","article-title":"On the role of 4-hydroxynonenal in health and disease","volume":"1852","author":"Csala","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"230","DOI":"10.2174\/09298673113209990181","article-title":"4-hydroxynonenal in the pathogenesis and progression of human diseases","volume":"21","author":"Shoeb","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1161\/01.CIR.0000018605.14470.DD","article-title":"Carvedilol decreases elevated oxidative stress in human failing myocardium","volume":"105","author":"Nakamura","year":"2002","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tjem.2018.08.001","article-title":"User\u2019s guide to correlation coefficients","volume":"18","author":"Akoglu","year":"2018","journal-title":"Turk. J. Emerg. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/837\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:14:27Z","timestamp":1760134467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/3\/837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,5]]},"references-count":51,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["jcm11030837"],"URL":"https:\/\/doi.org\/10.3390\/jcm11030837","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,5]]}}}