{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T20:20:56Z","timestamp":1786393256590,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["FPF-14"],"award-info":[{"award-number":["FPF-14"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione Gigi &amp; Pupa Ferrari ONLUS","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}]},{"name":"Fondazione Gigi &amp; Pupa Ferrari ONLUS","award":["FPF-14"],"award-info":[{"award-number":["FPF-14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In heart failure, the biological and clinical connection between abnormal iron homeostasis, myocardial function, and prognosis is known; however, the expression profiles of iron-linked genes both at myocardial tissue and single-cell level are not well defined. Through publicly available bulk and single-nucleus RNA sequencing (RNA-seq) datasets of left ventricle samples from adult non-failed (NF) and dilated cardiomyopathy (DCM) subjects, we aim to evaluate the altered iron metabolism in a diseased condition, at the whole cardiac tissue and single-cell level. From the bulk RNA-seq data, we found 223 iron-linked genes expressed at the myocardial tissue level and 44 differentially expressed between DCM and NF subjects. At the single-cell level, at least 18 iron-linked expressed genes were significantly regulated in DCM when compared to NF subjects. Specifically, the iron metabolism in DCM cardiomyocytes is altered at several levels, including: (1) imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation), (2) increase of iron consumption to produce hemoglobin (HBA1\/2 up-regulation), (3) higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation), (4) lower cleavage of heme to Fe2+, biliverdin and carbon monoxide (HMOX2 down-regulation), and (5) positive regulation of hepcidin (BMP6 up-regulation).<\/jats:p>","DOI":"10.3390\/ijms24032887","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T03:47:33Z","timestamp":1675309653000},"page":"2887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"24","author":[{"given":"Ilaria","family":"Massaiu","sequence":"first","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeness","family":"Campodonico","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-7407","authenticated-orcid":false,"given":"Massimo","family":"Mapelli","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Salvioni","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Valerio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7746-8539","authenticated-orcid":false,"given":"Donato","family":"Moschetta","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"},{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-5300","authenticated-orcid":false,"given":"Veronika A.","family":"Myasoedova","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-6864","authenticated-orcid":false,"given":"Maria Domenica","family":"Cappellini","sequence":"additional","affiliation":[{"name":"UOC General Medicine, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Pompilio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-3379","authenticated-orcid":false,"given":"Paolo","family":"Poggio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiuseppe","family":"Agostoni","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/ejhf.1461","article-title":"Heart failure in cardiomyopathies: A position paper from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Polovina","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s40792-018-0549-6","article-title":"Long-term outcome of a dilated cardiomyopathy patient after mitral valve surgery combined with tissue-engineered myoblast sheets\u2014Report of a case","volume":"4","author":"Miyagawa","year":"2018","journal-title":"Surg. Case Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tenge, T., Roth, S., M\u2018Pembele, R., Buse, G.L., Boenner, F., Ball\u00e1zs, C., Tudorache, I., Boeken, U., Lichtenberg, A., and Neukirchen, M. (2022). Impact of Left Ventricular Assist Devices on Days Alive and Out of Hospital in Hemodynamically Stable Patients with End-Stage Heart Failure: A Propensity Score Matched Study. Life, 12.","DOI":"10.3390\/life12121966"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1016\/j.jacc.2016.03.590","article-title":"The Diagnosis and Evaluation of Dilated Cardiomyopathy","volume":"67","author":"Japp","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1093\/eurheartj\/ehq158","article-title":"Iron deficiency: An ominous sign in patients with systolic chronic heart failure","volume":"31","author":"Jankowska","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_7","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."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1002\/ehf2.13265","article-title":"Iron deficiency in heart failure","volume":"8","author":"Loncar","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_9","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. Biophys. Acta Mol. Basis Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1111\/hdi.12542","article-title":"Overview of iron metabolism in health and disease","volume":"21","author":"Dev","year":"2017","journal-title":"Hemodial. Int."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vogt, A.-C., Arsiwala, T., Mohsen, M., Vogel, M., Manolova, V., and Bachmann, M. (2021). On Iron Metabolism and Its Regulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094591"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1089\/ars.2007.1893","article-title":"Intracellular Iron Transport and Storage: From Molecular Mechanisms to Health Implications","volume":"10","author":"Mackenzie","year":"2008","journal-title":"Antioxid. Redox Signal."},{"key":"ref_13","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":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tox.2011.03.001","article-title":"Advances in metal-induced oxidative stress and human disease","volume":"283","author":"Jomova","year":"2011","journal-title":"Toxicology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sukhbaatar, N., and Weichhart, T. (2018). Iron Regulation: Macrophages in Control. Pharmaceuticals, 11.","DOI":"10.3390\/ph11040137"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Koz\u0142owska, B., Sochanowicz, B., Kraj, L., Palusi\u0144ska, M., Ko\u0142sut, P., Szyma\u0144ski, \u0141., Lewicki, S., Kruszewski, M., Za\u0142\u0119ska-Koci\u0119cka, M., and Leszek, P. (2022). Clinical and Molecular Aspects of Iron Metabolism in Failing Myocytes. Life, 12.","DOI":"10.3390\/life12081203"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jacbts.2019.08.009","article-title":"Iron and Heart Failure: Diagnosis, Therapies, and Future Directions","volume":"5","author":"Ghafourian","year":"2020","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ravingerov\u00e1, T., Kindernay, L., Bartekov\u00e1, M., Ferko, M., Adameov\u00e1, A., Zohdi, V., Bern\u00e1tov\u00e1, I., Ferenczyov\u00e1, K., and Lazou, A. (2020). The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217889"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fphar.2014.00124","article-title":"The physiological functions of iron regulatory proteins in iron homeostasis\u2014An update","volume":"5","author":"Zhang","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1002\/ejhf.1305","article-title":"Screening, diagnosis and treatment of iron deficiency in chronic heart failure: Putting the 2016 European Society of Cardiology heart failure guidelines into clinical practice","volume":"20","author":"McDonagh","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1093\/eurjpc\/zwaa112","article-title":"Prognostic role of transferrin saturation in heart failure patients","volume":"28","author":"Campodonico","year":"2021","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1056\/NEJMoa0908355","article-title":"Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency","volume":"361","author":"Anker","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1002\/ejhf.2628","article-title":"Intravenous iron therapy improves the hypercapnic ventilatory response and sleep disordered breathing in chronic heart failure","volume":"24","author":"Caravita","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1093\/eurheartj\/ehab234","article-title":"The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: The results of the AFFIRM-AHF study","volume":"42","author":"Jankowska","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e022853","DOI":"10.1161\/JAHA.121.022853","article-title":"Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans","volume":"11","author":"Zhang","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Alnuwaysir, R.I.S., Hoes, M.F., van Veldhuisen, D.J., van der Meer, P., and Beverborg, N.G. (2021). Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology. J. Clin. Med., 11.","DOI":"10.3390\/jcm11010125"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.freeradbiomed.2015.07.019","article-title":"Iron and oxidative stress in cardiomyopathy in thalassemia","volume":"88","author":"Berdoukas","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41569-022-00735-4","article-title":"The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease","volume":"20","author":"Fang","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1152\/physrev.00003.2016","article-title":"Heme Oxygenases in Cardiovascular Health and Disease","volume":"96","author":"Ayer","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3892\/mmr.2020.11145","article-title":"Integrated microarray analysis to identify potential biomarkers and therapeutic targets in dilated cardiomyopathy","volume":"22","author":"Zhang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s44161-022-00028-6","article-title":"Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure","volume":"1","author":"Koenig","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"865096","DOI":"10.3389\/fcvm.2022.865096","article-title":"Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy","volume":"9","author":"Zheng","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/ng1658","article-title":"Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells","volume":"37","author":"Ohgami","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1161\/HYPERTENSIONAHA.120.14752","article-title":"STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) Inhibits Pathological Cardiac Hypertrophy","volume":"76","author":"Li","year":"2020","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.toxlet.2005.03.004","article-title":"Free heme toxicity and its detoxification systems in human","volume":"157","author":"Kumar","year":"2005","journal-title":"Toxicol. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"241","DOI":"10.14348\/molcells.2014.2344","article-title":"Postmortem mRNA expression patterns in left ventricular myocardial tissues and their implications for forensic diagnosis of sudden cardiac death","volume":"37","author":"Son","year":"2014","journal-title":"Mol. Cells"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1016\/j.jacc.2013.02.012","article-title":"Heme Levels Are Increased in Human Failing Hearts","volume":"61","author":"Khechaduri","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1124\/jpet.109.158352","article-title":"Heme Oxygenase-2 Deletion Causes Endothelial Cell Activation Marked by Oxidative Stress, Inflammation, and Angiogenesis","volume":"331","author":"Bellner","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9452","DOI":"10.1074\/jbc.M109.077230","article-title":"Enhanced Translation of Heme Oxygenase-2 Preserves Human Endothelial Cell Viability during Hypoxia","volume":"285","author":"He","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1111\/jcmm.12389","article-title":"Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression","volume":"18","author":"Lundvig","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/ng.335","article-title":"BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism","volume":"41","author":"Andriopoulos","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_45","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_46","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_47","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.bbrc.2016.08.034","article-title":"CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation","volume":"478","author":"Yuan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.canlet.2018.06.018","article-title":"CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer","volume":"432","author":"Kim","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.redox.2020.101619","article-title":"The BRD7-P53-SLC25A28 axis regulates ferroptosis in hepatic stellate cells","volume":"36","author":"Zhang","year":"2020","journal-title":"Redox Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/s41467-018-03751-6","article-title":"Massive mining of publicly available RNA-seq data from human and mouse","volume":"9","author":"Lachmann","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1111\/aor.13770","article-title":"A new pathophysiology in heart failure patients","volume":"44","author":"Sciomer","year":"2020","journal-title":"Artif. Organs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1093\/bioinformatics\/btx795","article-title":"DaMiRseq-an R\/Bioconductor package for data mining of RNA-Seq data: Normalization, feature selection and classification","volume":"34","author":"Chiesa","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41556-019-0446-7","article-title":"Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function","volume":"22","author":"Wang","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/nbt0308-303","article-title":"What is principal component analysis?","volume":"26","author":"Ringner","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41420-021-00579-w","article-title":"Ferroptosis: A cell death connecting oxidative stress, inflammation and cardiovascular diseases","volume":"7","author":"Yu","year":"2021","journal-title":"Cell Death Discov."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:22:06Z","timestamp":1760120526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032887"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032887","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]}}}