{"doi":"10.3390/ijms26146766","title":"Early-Stage Alcoholic Cardiomyopathy Highlighted by Metabolic Remodeling, Oxidative Stress, and Cardiac Myosin Dysfunction in Male Rats","abstract":"Chronic ethanol use can lead to alcoholic cardiomyopathy (ACM), while the impact on the molecular and cellular aspects of the myocardium is unclear. Accordingly, male Sprague-Dawley rats were exposed to an ethanol-containing diet for 16 weeks and compared with a control group that was fed an isocaloric diet. Histological measurements from H&E slides revealed no significant differences in cell size. A proteomic approach revealed that alcohol exposure leads to enhanced mitochondrial lipid metabolism, and electron microscopy revealed impairments in mitochondrial morphology/density. Cardiac myosin purified from the hearts of ethanol-exposed animals demonstrated a 15% reduction in high-salt ATPase activity, with no significant changes in the in vitro motility and low-salt ATPase or formation of the super-relaxed (SRX) state. A protein carbonyl assay indicated a 20% increase in carbonyl incorporation, suggesting that alcohol may impact cardiac myosin through oxidative stress mechanisms. In vitro oxidation of healthy cardiac myosin revealed a dramatic decline in ATPase activity and in vitro motility, demonstrating a link between myosin protein oxidation and myosin mechanochemistry. Collectively, this study suggests alcohol-induced metabolic remodeling may be the initial insult that eventually leads to defects in the contractile machinery in the myocardium of ACM hearts.","journal":"International Journal of Molecular Sciences","year":2025,"id":528486,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":577295,"name":"Jinghua Ge","orcid":"0000-0002-5820-1521","position":1,"is_corresponding":false},{"id":1406819,"name":"Adrien P. Chen","orcid":null,"position":2,"is_corresponding":false},{"id":774934,"name":"Neil B. Wood","orcid":"0000-0001-6352-6358","position":3,"is_corresponding":false},{"id":706056,"name":"Skylar M.L. Bodt","orcid":"0000-0002-5794-6927","position":4,"is_corresponding":false},{"id":453863,"name":"Allyson L. Toro","orcid":null,"position":5,"is_corresponding":false},{"id":1104239,"name":"Alexandra Evans","orcid":"0000-0002-4055-7300","position":6,"is_corresponding":false},{"id":1406820,"name":"Omid Golestanian","orcid":null,"position":7,"is_corresponding":false},{"id":868845,"name":"Md Shahrier Amin","orcid":"0000-0003-3791-508X","position":8,"is_corresponding":false},{"id":1406821,"name":"Anne M. Pruznak","orcid":null,"position":9,"is_corresponding":false},{"id":271579,"name":"Nelli Mnatsakanyan","orcid":"0000-0001-5363-7409","position":10,"is_corresponding":false},{"id":320868,"name":"Yuval Silberman","orcid":"0000-0002-4694-4053","position":11,"is_corresponding":false},{"id":452865,"name":"Michael D. Dennis","orcid":"0000-0002-0645-6864","position":12,"is_corresponding":false},{"id":457219,"name":"Michael J. Previs","orcid":"0000-0002-8851-7439","position":13,"is_corresponding":false},{"id":374248,"name":"Charles H. Lang","orcid":"0000-0002-3260-7363","position":14,"is_corresponding":false},{"id":577296,"name":"Christopher M. Yengo","orcid":"0000-0003-3987-9019","position":15,"is_corresponding":false},{"id":774932,"name":"David V. Rasicci","orcid":"0000-0003-3891-0694","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40725013","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":[]}