{"doi":"10.1016/j.celrep.2020.107886","title":"Modeling Secondary Iron Overload Cardiomyopathy with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes","abstract":"Excessive iron accumulation in the heart causes iron overload cardiomyopathy (IOC), which initially presents as diastolic dysfunction and arrhythmia but progresses to systolic dysfunction and end-stage heart failure when left untreated. However, the mechanisms of iron-related cardiac injury and how iron accumulates in human cardiomyocytes are not well understood. Herein, using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we model IOC and screen for drugs to rescue the iron overload phenotypes. Human iPSC-CMs under excess iron exposure recapitulate early-stage IOC, including oxidative stress, arrhythmia, and contractile dysfunction. We find that iron-induced changes in calcium kinetics play a critical role in dysregulation of CM functions. We identify that ebselen, a selective divalent metal transporter 1 (DMT1) inhibitor and antioxidant, could prevent the observed iron overload phenotypes, supporting the role of DMT1 in iron uptake into the human myocardium. These results suggest that ebselen may be a potential preventive and therapeutic agent for treating patients with secondary iron overload.","journal":"Cell Reports","year":2020,"id":91163,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":456740,"name":"Hyoju Yi","orcid":"0000-0002-6786-4327","position":1,"is_corresponding":false},{"id":456741,"name":"Dilip Thomas","orcid":"0000-0001-7427-5523","position":2,"is_corresponding":false},{"id":229028,"name":"Chi Keung Lam","orcid":"0000-0003-4565-9426","position":3,"is_corresponding":false},{"id":396382,"name":"Nadjet Belbachir","orcid":null,"position":4,"is_corresponding":false},{"id":241112,"name":"Lei Tian","orcid":"0000-0002-7485-9366","position":5,"is_corresponding":false},{"id":319195,"name":"Xulei Qin","orcid":null,"position":6,"is_corresponding":false},{"id":456742,"name":"Jessica Malisa","orcid":"0000-0002-7877-2428","position":7,"is_corresponding":false},{"id":424629,"name":"Edward Lau","orcid":"0000-0001-9083-5922","position":8,"is_corresponding":false},{"id":241148,"name":"David T. Paik","orcid":"0000-0002-7830-312X","position":9,"is_corresponding":false},{"id":456743,"name":"Youngkyun Kim","orcid":"0000-0003-3078-6852","position":10,"is_corresponding":false},{"id":457994,"name":"Beatrice SeungHye Choi","orcid":null,"position":11,"is_corresponding":false},{"id":278890,"name":"Nazish Sayed","orcid":"0000-0002-8229-721X","position":12,"is_corresponding":false},{"id":278897,"name":"Karim Sallam","orcid":"0000-0003-3469-6571","position":13,"is_corresponding":false},{"id":299767,"name":"Ronglih Liao","orcid":"0000-0002-9598-9020","position":14,"is_corresponding":false},{"id":12998,"name":"Joseph C. Wu","orcid":"0000-0002-6068-8041","position":15,"is_corresponding":false},{"id":242372,"name":"June‐Wha Rhee","orcid":"0000-0002-7044-2985","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T22:28:45.409789Z","pmid":"32668256","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}