{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:02:36Z","timestamp":1777532556424,"version":"3.51.4"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"28","license":[{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1118\/1036"],"award-info":[{"award-number":["SFB 1118\/1036"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Faculty of Heidelberg"},{"DOI":"10.13039\/100008594","name":"European Hematology Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Whether and how iron affects the progression of atherosclerosis remains highly debated. Here, we investigate susceptibility to atherosclerosis in a mouse model (ApoE\u2212\/\u2212 FPNwt\/C326S), which develops the disease in the context of elevated non-transferrin bound serum iron (NTBI).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Compared with normo-ferremic ApoE\u2212\/\u2212 mice, atherosclerosis is profoundly aggravated in iron-loaded ApoE\u2212\/\u2212 FPNwt\/C326S mice, suggesting a pro-atherogenic role for iron. Iron heavily deposits in the arterial media layer, which correlates with plaque formation, vascular oxidative stress and dysfunction. Atherosclerosis is exacerbated by iron-triggered lipid profile alterations, vascular permeabilization, sustained endothelial activation, elevated pro-atherogenic inflammatory mediators, and reduced nitric oxide availability. NTBI causes iron overload, induces reactive oxygen species production and apoptosis in cultured vascular cells, and stimulates massive MCP-1-mediated monocyte recruitment, well-established mechanisms contributing to atherosclerosis. NTBI-mediated toxicity is prevented by transferrin- or chelator-mediated iron scavenging. Consistently, a low-iron diet and iron chelation therapy strongly improved the course of the disease in ApoE\u2212\/\u2212 FPNwt\/C326S mice. Our results are corroborated by analyses of serum samples of haemochromatosis patients, which show an inverse correlation between the degree of iron depletion and hallmarks of endothelial dysfunction and inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data demonstrate that NTBI-triggered iron overload aggravates atherosclerosis and unravel a causal link between NTBI and the progression of atherosclerotic lesions. Our findings support clinical applications of iron restriction in iron-loaded individuals to counteract iron-aggravated vascular dysfunction and atherosclerosis.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz112","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T20:36:43Z","timestamp":1551991003000},"page":"2681-2695","source":"Crossref","is-referenced-by-count":254,"title":["Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction"],"prefix":"10.1093","volume":"41","author":[{"given":"Francesca","family":"Vinchi","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Otto Meyerhof Zentrum , Im Neuenheimer Feld 350, 69120 Heidelberg, Germany"},{"name":"Iron Homeostasis Group, Molecular Medicine Partnership Unit (MMPU) , Heidelberg University, Im Neuenheimer Feld 350, 69120, Heidelberg & European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany"},{"name":"New York Blood Center (NYBC), Iron Research Program, Lindsley F. Kimball Research Institute (LFKRI) , 310 East 67th Street, 10065, New York, NY, USA"},{"name":"Institute of Medical Biometry and Informatics (IMBI), University Hospital Heidelberg , Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany"}]},{"given":"Graca","family":"Porto","sequence":"additional","affiliation":[{"name":"Centro Hospitalar do Porto-Hospital Santo Ant\u00f3nio , Largo do Prof. Abel Slazar, 4099-001 Porto, Portugal"},{"name":"Instituto de Biologia Molecular e Celular & Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto , Rua Alfredo Allen, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto , Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Andreas","family":"Simmelbauer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Otto Meyerhof Zentrum , Im Neuenheimer Feld 350, 69120 Heidelberg, Germany"},{"name":"Iron Homeostasis Group, Molecular Medicine Partnership Unit (MMPU) , Heidelberg University, Im Neuenheimer Feld 350, 69120, Heidelberg & European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany"}]},{"given":"Sandro","family":"Altamura","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Otto Meyerhof Zentrum , Im Neuenheimer Feld 350, 69120 Heidelberg, Germany"},{"name":"Iron Homeostasis Group, Molecular Medicine Partnership Unit (MMPU) , Heidelberg University, Im Neuenheimer Feld 350, 69120, Heidelberg & European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany"},{"name":"Institute of Medical Biometry and Informatics (IMBI), University Hospital Heidelberg , Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany"}]},{"given":"Sara T","family":"Passos","sequence":"additional","affiliation":[{"name":"New York Blood Center (NYBC), Iron Research Program, Lindsley F. Kimball Research Institute (LFKRI) , 310 East 67th Street, 10065, New York, NY, USA"}]},{"given":"Maciej","family":"Garbowski","sequence":"additional","affiliation":[{"name":"Hematology Department, University College London Cancer Institute , London, aul O'Gorman Bld, 72 Huntley Street, WC1E 6DD, London, UK"}]},{"given":"Andr\u00e9 M N","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Quimica e Bioquimica, REQUIMITE-LAQV, Faculdade de Ciencias, University of Porto , Rua Do Campo Alegre, 4169-007 Porto, Portugal"}]},{"given":"Sebastian","family":"Spaich","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumonology, University of Heidelberg , Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}]},{"given":"Svenja E","family":"Seide","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Informatics (IMBI), University Hospital Heidelberg , Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany"}]},{"given":"Richard","family":"Sparla","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Otto Meyerhof Zentrum , Im Neuenheimer Feld 350, 69120 Heidelberg, Germany"}]},{"given":"Matthias W","family":"Hentze","sequence":"additional","affiliation":[{"name":"Iron Homeostasis Group, Molecular Medicine Partnership Unit (MMPU) , Heidelberg University, Im Neuenheimer Feld 350, 69120, Heidelberg & European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory (EMBL) , Meyerhofstrasse 1, 69117 Heidelberg, Germany"}]},{"given":"Martina U","family":"Muckenthaler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Otto Meyerhof Zentrum , Im Neuenheimer Feld 350, 69120 Heidelberg, Germany"},{"name":"Iron Homeostasis Group, Molecular Medicine Partnership Unit (MMPU) , Heidelberg University, Im Neuenheimer Feld 350, 69120, Heidelberg & European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany"},{"name":"European Molecular Biology Laboratory (EMBL) , Meyerhofstrasse 1, 69117 Heidelberg, Germany"}]}],"member":"286","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"2022102608274385100_ehz112-B1","doi-asserted-by":"crossref","first-page":"94.","DOI":"10.3389\/fphar.2014.00094","article-title":"Atherogenesis and iron: from epidemiology to cellular level","volume":"5","author":"Vinchi","year":"2014","journal-title":"Front Pharmacol"},{"key":"2022102608274385100_ehz112-B2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.cmet.2014.07.007","article-title":"Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload","volume":"20","author":"Altamura","year":"2014","journal-title":"Cell Metab"},{"key":"2022102608274385100_ehz112-B3","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2016.12.034","article-title":"A red carpet for iron metabolism","volume":"168","author":"Muckenthaler","year":"2017","journal-title":"Cell"},{"key":"2022102608274385100_ehz112-B4","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S0140-6736(81)92463-6","article-title":"Iron and the sex difference in heart disease risk","volume":"1","author":"Sullivan","year":"1981","journal-title":"Lancet"},{"key":"2022102608274385100_ehz112-B5","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1067\/mhj.2003.142","article-title":"Are menstruating women protected from heart disease because of, or in spite of, estrogen? 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