{"doi":"10.1038/s41598-020-71079-7","title":"Ischemia reperfusion injury provokes adverse left ventricular remodeling in dysferlin-deficient hearts through a pathway that involves TIRAP dependent signaling","abstract":"Abstract Cardiac myocytes have multiple cell autonomous mechanisms that facilitate stabilization and repair of damaged sarcolemmal membranes following myocardial injury. Dysferlin is a protein which facilitates membrane repair by promoting membrane resealing. Although prior studies have shown that dysferlin-deficient ( Dysf −/− ) mouse hearts have an impaired recovery from acute ischemia/reperfusion (I/R) injury ex vivo, the role of dysferlin in mediating the recovery from myocardial injury in vivo is unknown. Here we show that Dysf −/− mice develop adverse LV remodeling following I/R injury secondary to the collateral damage from sustained myocardial inflammation within the infarct zone. Backcrossing Dysf −/− mice with mice lacking signaling through the Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein ( Tirap −/− ), attenuated inflammation and abrogated adverse LV remodeling following I/R injury. Subsequent studies using Poloxamer 188 (P188), a membrane resealing reagent, demonstrated that P188 did not attenuate inflammation nor prevent adverse LV remodeling in Dysf −/− mice following I/R injury. Viewed together these studies reveal a previously unappreciated role for the importance of membrane sealing and the resolution of inflammation following myocardial injury.","journal":"Scientific Reports","year":2020,"id":82919,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"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":258404,"name":"Carla J. Weinheimer","orcid":"0000-0001-7922-7512","position":1,"is_corresponding":false},{"id":258403,"name":"Attila Kovács","orcid":"0000-0003-2320-6434","position":2,"is_corresponding":false},{"id":230325,"name":"Jesse W. Williams","orcid":"0000-0003-3815-0891","position":3,"is_corresponding":false},{"id":61573,"name":"Gwendalyn J. Randolph","orcid":"0000-0001-9045-1195","position":4,"is_corresponding":false},{"id":426933,"name":"Wenlong Jiang","orcid":"0000-0001-9948-4196","position":5,"is_corresponding":false},{"id":427630,"name":"Philip M. Barger","orcid":null,"position":6,"is_corresponding":false},{"id":233712,"name":"Douglas L. Mann","orcid":"0000-0002-2516-0145","position":7,"is_corresponding":false},{"id":282755,"name":"Sarah Evans","orcid":"0000-0002-6390-6729","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T21:53:48.608934Z","pmid":"32839504","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":[]}