{"doi":"10.1242/dmm.050487","title":"Physiological stress improves stem cell modeling of dystrophic cardiomyopathy","abstract":"Heart failure contributes to Duchenne muscular dystrophy (DMD), which arises from mutations that ablate dystrophin, rendering the plasma membrane prone to disruption. Cardiomyocyte membrane breakdown in patients with DMD yields a serum injury profile similar to other types of myocardial injury with the release of creatine kinase and troponin isoforms. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly useful but can be improved. We generated hiPSC-CMs from a patient with DMD and subjected these cells to equibiaxial mechanical strain to mimic in vivo stress. Compared to healthy cells, DMD hiPSC-CMs demonstrated greater susceptibility to equibiaxial strain after 2 h at 10% strain. We generated an aptamer-based profile of proteins released from hiPSC-CMs both at rest and subjected to strain and identified a strong correlation in the mechanical stress-induced proteome from hiPSC-CMs and serum from patients with DMD. We exposed hiPSC-CMs to recombinant annexin A6, a protein resealing agent, and found reduced biomarker release in DMD and control hiPSC-CMs subjected to strain. Thus, the application of mechanical strain to hiPSC-CMs produces a model that reflects an in vivo injury profile, providing a platform to assess pharmacologic intervention.","journal":"Disease Models & Mechanisms","year":2023,"id":376171,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9418,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707614,"name":"Alexander B. Willis","orcid":"0000-0003-4145-5821","position":1,"is_corresponding":false},{"id":1101731,"name":"Jodi L. Curtin","orcid":null,"position":2,"is_corresponding":false},{"id":634578,"name":"Ansel P. Amaral","orcid":"0000-0003-0897-5198","position":3,"is_corresponding":false},{"id":1138976,"name":"Kyle Dittloff","orcid":"0000-0003-3824-8469","position":4,"is_corresponding":false},{"id":992263,"name":"Sloane I. Harris","orcid":null,"position":5,"is_corresponding":false},{"id":1138977,"name":"Ivana A. Chychula","orcid":"0009-0003-6617-752X","position":6,"is_corresponding":false},{"id":43023,"name":"Cory Holgren","orcid":null,"position":7,"is_corresponding":false},{"id":245967,"name":"Paul W. Burridge","orcid":"0000-0001-9616-0006","position":8,"is_corresponding":false},{"id":1138978,"name":"Brenda Russell","orcid":"0000-0002-4847-5836","position":9,"is_corresponding":false},{"id":554009,"name":"Alexis R. Demonbreun","orcid":"0000-0001-6823-125X","position":10,"is_corresponding":false},{"id":297686,"name":"Elizabeth M. McNally","orcid":"0000-0002-1221-719X","position":11,"is_corresponding":false},{"id":991948,"name":"Dominic E. Fullenkamp","orcid":"0000-0001-7627-7119","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:16:28.318749Z","pmid":"38050701","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":[]}