{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:36:11Z","timestamp":1792064171387,"version":"4.4.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T00:00:00Z","timestamp":1567814400000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cardiomyopathic manifestations induced by continuous blood transfusion are the leading cause of death among patients with thalassemia major (TM). Despite introduction of chelation therapy, heart failure after cardiomyopathic manifestations is still a major threat to patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a search of relevant English-language literature, retrieving publications from the PubMed database and the Google Scholar search engine (2005\u20132018). We used \u201cthalassemia major\u201d, \u201ccardiomyopathy\u201d, \u201ciron overload\u201d, \u201ccardiac magnetic resonance T2\u201d \u201cchelation therapy\u201d, and \u201ciron burden\u201d as keywords.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The results of the studies we found suggest that cardiac hepcidin is a major regulator of iron homeostasis in cardiac tissue. Unlike previous assumptions, the heart appears to have a limited regeneration capability, originating from a small population of hypoxic cardiomyocytes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Oxygen levels determine cardiomyocyte gene-expression patterns. Upregulation of cardiac hepcidin in hypoxia preserves cardiomyocytes from forming out of reactive oxygen species catalyzed by free cellular iron in cardiomyocytes. Using the limited regeneration capacity of cardiac cells and gaining further understanding of the cellular aspects of cardiomyopathic manifestations may help health care professionals to develop new therapeutic strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/labmed\/lmz052","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T18:17:03Z","timestamp":1561486623000},"source":"Crossref","is-referenced-by-count":3,"title":["Cardiomyopathy in Thalassemia: Quick Review from Cellular Aspects to Diagnosis and Current Treatments"],"prefix":"10.1093","author":[{"given":"Majid","family":"Ghanavat","sequence":"first","affiliation":[{"name":"Child Growth & Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habib","family":"Haybar","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-5282","authenticated-orcid":false,"given":"Seyed Mohammad Sadegh","family":"Pezeshki","sequence":"additional","affiliation":[{"name":"Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Shahjahani","sequence":"additional","affiliation":[{"name":"Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosein","family":"Jodat","sequence":"additional","affiliation":[{"name":"Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milad","family":"Elyasi","sequence":"additional","affiliation":[{"name":"Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-5594","authenticated-orcid":false,"given":"Najmaldin","family":"Saki","sequence":"additional","affiliation":[{"name":"Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran"},{"name":"Child Growth & Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,2]]},"reference":[{"key":"2019090622345734600_CIT0001","doi-asserted-by":"crossref","first-page":"1559s","DOI":"10.3945\/ajcn.117.155804","article-title":"Current understanding of iron homeostasis","volume":"106","author":"Anderson","year":"2017","journal-title":"Am J Clin Nut."},{"issue":"3","key":"2019090622345734600_CIT0002","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bcmd.2011.07.002","article-title":"Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials","volume":"47","author":"Maggio","year":"2011","journal-title":"Blood Cells Mol Dis."},{"issue":"12","key":"2019090622345734600_CIT0003","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1136\/heartjnl-2012-302857","article-title":"Thalassaemia major and the heart: a toxic cardiomyopathy tamed?","volume":"99","author":"Walker","year":"2013","journal-title":"Heart."},{"key":"2019090622345734600_CIT0004","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ejphar.2015.08.017","article-title":"Current and future treatment strategies for iron overload cardiomyopathy","volume":"765","author":"Wongjaikam","year":"2015","journal-title":"Eur J Pharmacol."},{"issue":"2\u20133","key":"2019090622345734600_CIT0005","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jtemb.2012.03.015","article-title":"Intestinal iron absorption","volume":"26","author":"Fuqua","year":"2012","journal-title":"J Trace Elem Med Biol."},{"issue":"1","key":"2019090622345734600_CIT0006","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."},{"issue":"10","key":"2019090622345734600_CIT0007","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":"Lakhal-Littleton","year":"2015","journal-title":"Proc Nat Acad Sci USA."},{"issue":"4","key":"2019090622345734600_CIT0008","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1152\/japplphysiol.00237.2017","article-title":"The interplay between iron and oxygen homeostasis with a particular focus on the heart","volume":"123","author":"Lakhal-Littleton","year":"2017","journal-title":"J Appl Physiol (1985)."},{"key":"2019090622345734600_CIT0009","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.freeradbiomed.2018.08.010","article-title":"Mechanisms of cardiac iron homeostasis and their importance to heart function","volume":"133","author":"Lakhal-Littleton","year":"2019","journal-title":"Free Radic Biol Med."},{"issue":"3","key":"2019090622345734600_CIT0010","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/CIRCHEARTFAILURE.109.913863","article-title":"Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives","volume":"3","author":"Kremastinos","year":"2010","journal-title":"Circ Heart Fail."},{"issue":"3","key":"2019090622345734600_CIT0011","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1172\/JCI200524408","article-title":"Oxygen, oxidative stress, hypoxia, and heart failure","volume":"115","author":"Giordano","year":"2005","journal-title":"J Clin Invest."},{"issue":"8","key":"2019090622345734600_CIT0012","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1093\/cvr\/cvy278","article-title":"Protein kinase C binding protein 1(PRKCBP1) inhibits hypoxia inducible factor 1 (HIF-1) in the heart","volume":"115","author":"Schunke","year":"2019","journal-title":"Cardiovasc Res."},{"issue":"4","key":"2019090622345734600_CIT0013","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/apm.12822","article-title":"Oxidative stress in normal hematopoietic stem cells and leukemia","volume":"126","author":"Samimi","year":"2018","journal-title":"APMIS."},{"key":"2019090622345734600_CIT0014","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19804","article-title":"An essential cell-autonomous role for hepcidin in cardiac iron homeostasis","volume":"5","author":"Lakhal-Littleton","year":"2016","journal-title":"eLife."},{"issue":"3","key":"2019090622345734600_CIT0015","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 Invest."},{"issue":"1","key":"2019090622345734600_CIT0016","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1745-6673-9-11","article-title":"Silencing of hepcidin enforces the apoptosis in iron-induced human cardiomyocytes","volume":"9","author":"Hsieh","year":"2014","journal-title":"J Occup Med Toxicol."},{"issue":"7598","key":"2019090622345734600_CIT0017","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/nature16177","article-title":"Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart","volume":"532","author":"Kimura","year":"2016","journal-title":"Nature."},{"issue":"7636","key":"2019090622345734600_CIT0018","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature20173","article-title":"Hypoxia induces heart regeneration in adult mice","volume":"541","author":"Nakada","year":"2017","journal-title":"Nature"},{"issue":"10","key":"2019090622345734600_CIT0019","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.acvd.2017.06.001","article-title":"Hypoxia and heart regeneration: a new paradoxical approach for cardioprotection","volume":"110","author":"Rochette","year":"2017","journal-title":"Arch Cardiovasc Dis."},{"issue":"7","key":"2019090622345734600_CIT0020","first-page":"651","article-title":"The expression of Smad signaling pathway in myocardium and potential therapeutic effects","volume":"32","author":"Duan","year":"2017","journal-title":"Histol Histopathol."},{"issue":"11","key":"2019090622345734600_CIT0021","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.cardfail.2010.05.009","article-title":"Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment","volume":"16","author":"Murphy","year":"2010","journal-title":"J Card Fail."},{"issue":"20","key":"2019090622345734600_CIT0022","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1161\/CIRCULATIONAHA.111.050773","article-title":"Iron overload cardiomyopathy in clinical practice","volume":"124","author":"Kremastinos","year":"2011","journal-title":"Circulation."},{"issue":"4","key":"2019090622345734600_CIT0023","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.hoc.2014.04.002","article-title":"Use of magnetic resonance imaging to monitor iron overload","volume":"28","author":"Wood","year":"2014","journal-title":"Hematol Oncol Clin North Am."},{"issue":"1","key":"2019090622345734600_CIT0024","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3324\/haematol.2010.034397","article-title":"In search of the optimal iron chelation therapy for patients with thalassemia major","volume":"96","author":"Berdoukas","year":"2011","journal-title":"Haematologica."},{"issue":"12","key":"2019090622345734600_CIT0025","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1016\/j.clinthera.2015.10.001","article-title":"Iron chelation in thalassemia major","volume":"37","author":"Borgna-Pignatti","year":"2015","journal-title":"Clin Ther."},{"issue":"2","key":"2019090622345734600_CIT0026","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1586\/17474086.2016.1126176","article-title":"Clinical monitoring and management of complications related to chelation therapy in patients with \u03b2-thalassemia","volume":"9","author":"Saliba","year":"2016","journal-title":"Expert Rev Hematol."},{"issue":"2","key":"2019090622345734600_CIT0027","first-page":"168","article-title":"Comparison of deferiprone to deferasirox and deferoxamine to cardiac and hepatic T2* MRI in thalassemia patients: evidence-based case report","volume":"50","author":"Wahidiyat","year":"2018","journal-title":"Acta Med Indones."},{"issue":"12","key":"2019090622345734600_CIT0028","doi-asserted-by":"crossref","first-page":"e82662","DOI":"10.1371\/journal.pone.0082662","article-title":"Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials","volume":"8","author":"Xia","year":"2013","journal-title":"PLoS One."},{"issue":"9","key":"2019090622345734600_CIT0029","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1182\/blood-2005-08-3430","article-title":"A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with \u03b2-thalassemia","volume":"107","author":"Cappellini","year":"2006","journal-title":"Blood."},{"issue":"3","key":"2019090622345734600_CIT0030","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/10976640600698155","article-title":"Myocardial iron loading in patients with thalassemia major on deferoxamine chelation","volume":"8","author":"Tanner","year":"2006","journal-title":"J Cardiovasc Magn Reson."},{"issue":"1","key":"2019090622345734600_CIT0031","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bcmd.2011.03.007","article-title":"Oral chelators in transfusion-dependent thalassemia major patients may prevent or reverse iron overload complications","volume":"47","author":"Farmaki","year":"2011","journal-title":"Blood Cells Mol Dis."},{"key":"2019090622345734600_CIT0032","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fphar.2014.00045","article-title":"Labile iron in cells and body fluids: physiology, pathology, and pharmacology","volume":"5","author":"Cabantchik","year":"2014","journal-title":"Front Pharmacol."},{"issue":"7","key":"2019090622345734600_CIT0033","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/ajh.25103","article-title":"The effect of iron chelation therapy on overall survival in sickle cell disease and \u03b2-thalassemia: a systematic review","volume":"93","author":"Ballas","year":"2018","journal-title":"Am J Hematol."},{"issue":"12","key":"2019090622345734600_CIT0034","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."},{"issue":"3","key":"2019090622345734600_CIT0035","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bcmd.2013.06.001","article-title":"Longitudinal analysis of heart and liver iron in thalassemia major patients according to chelation treatment","volume":"51","author":"Danjou","year":"2013","journal-title":"Blood Cells Mol Dis."},{"issue":"4","key":"2019090622345734600_CIT0036","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1182\/blood-2010-11-316646","article-title":"Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years\u2019 follow-up","volume":"118","author":"Cappellini","year":"2011","journal-title":"Blood."},{"issue":"1","key":"2019090622345734600_CIT0037","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3109\/08880018.2013.861046","article-title":"Efficacy and safety of deferasirox in beta-thalassemia major patients in Iran: a prospective study from a single referral center in Iran","volume":"31","author":"Alavi","year":"2014","journal-title":"Ped Hematol Oncol."},{"issue":"9","key":"2019090622345734600_CIT0038","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s00277-012-1480-8","article-title":"Cardiac iron removal and functional cardiac improvement by different iron chelation regimens in thalassemia major patients","volume":"91","author":"Cassinerio","year":"2012","journal-title":"Ann Hematol."},{"issue":"2","key":"2019090622345734600_CIT0039","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/tme.12014","article-title":"Cardiac iron measurement and iron chelation therapy in patients with \u03b2 thalassaemia major: experience from Taiwan","volume":"23","author":"Lu","year":"2013","journal-title":"Transfus Med."},{"issue":"2","key":"2019090622345734600_CIT0040","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.bcmd.2012.10.006","article-title":"Combined chelation therapy with deferasirox and deferoxamine in thalassemia","volume":"50","author":"Lal","year":"2013","journal-title":"Blood Cells Mol Dis."},{"issue":"9\u201310","key":"2019090622345734600_CIT0041","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10528-015-9687-8","article-title":"The influence of polymorphisms in disease severity in \u03b2-thalassemia","volume":"53","author":"Mohammdai-Asl","year":"2015","journal-title":"Biochem Genet."},{"issue":"2","key":"2019090622345734600_CIT0042","first-page":"193","article-title":"Molecular aspects of bone resorption in \u03b2-thalassemia major","volume":"17","author":"Saki","year":"2015","journal-title":"Cell J."},{"issue":"3","key":"2019090622345734600_CIT0043","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00277-013-1876-0","article-title":"Low prevalence of cardiac siderosis in heavily iron loaded Egyptian thalassemia major patients","volume":"93","author":"El Beshlawy","year":"2014","journal-title":"Ann Hematol"},{"issue":"12","key":"2019090622345734600_CIT0044","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1002\/ajh.23844","article-title":"Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with \u03b2-thalassemia major","volume":"89","author":"Casale","year":"2014","journal-title":"Am J Hematol."},{"issue":"1","key":"2019090622345734600_CIT0045","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.116.003456","article-title":"Females are protected from iron-overload cardiomyopathy independent of iron metabolism: key role of oxidative stress","volume":"6","author":"Das","year":"2017","journal-title":"J Am Heart Assoc."}],"container-title":["Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/labmed\/advance-article-pdf\/doi\/10.1093\/labmed\/lmz052\/29807309\/lmz052.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"}],"deposited":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T02:35:16Z","timestamp":1567823716000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/labmed\/advance-article\/doi\/10.1093\/labmed\/lmz052\/5542818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,2]]},"references-count":45,"URL":"https:\/\/doi.org\/10.1093\/labmed\/lmz052","relation":{},"ISSN":["0007-5027","1943-7730"],"issn-type":[{"value":"0007-5027","type":"print"},{"value":"1943-7730","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,2]]},"article-number":"lmz052"}}