{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:53:58Z","timestamp":1790949238710,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"nextGENERATION Medical Scientist program from Else Kr\u00f6ner-Fresenius Stiftung","award":["REVERSE"],"award-info":[{"award-number":["REVERSE"]}]},{"name":"nextGENERATION Medical Scientist program from Else Kr\u00f6ner-Fresenius Stiftung","award":["101054460"],"award-info":[{"award-number":["101054460"]}]},{"name":"EU","award":["REVERSE"],"award-info":[{"award-number":["REVERSE"]}]},{"name":"EU","award":["101054460"],"award-info":[{"award-number":["101054460"]}]},{"name":"ERC","award":["REVERSE"],"award-info":[{"award-number":["REVERSE"]}]},{"name":"ERC","award":["101054460"],"award-info":[{"award-number":["101054460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic heart disease is the leading cause of death worldwide. Reduced oxygen supply and myocardial hypoxia lead to tissue damage and impairment of the heart function. To the best of our knowledge, the primary functional effects of hypoxia in the multicellular model of living myocardial slices (LMSs) have not been investigated so far. In this study, we analyzed force generation, ultrastructure, gene expression, and proteome changes in rat LMS after 24 h of ex vivo culture in normal and reduced levels of oxygen (O2). We observed a significant reduction in absolute force and a slowdown of force kinetics as well as an increase in cardiomyocyte apoptosis and myofibrillar and mitochondrial damage, as well as transcriptomic changes. Proteome analysis revealed the deregulation of proteins involved in metabolic processes, hypoxic response, and neutralizing of reactive oxygen species. Our results indicate that hypoxia induces substantial primary changes in heart tissue, which are independent of perfusion and immune responses. Our new LMS model could serve as a screening system for drug development and new mechanistic insights.<\/jats:p>","DOI":"10.3390\/ijms26010218","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:51:57Z","timestamp":1735631517000},"page":"218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Prolonged Hypoxia in Rat Living Myocardial Slices Affects Function, Expression, and Structure"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9455-9412","authenticated-orcid":false,"given":"Florian J. G.","family":"Waleczek","sequence":"first","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"},{"name":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7475-5367","authenticated-orcid":false,"given":"Giuseppe","family":"Cipriano","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas A.","family":"Haas","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Garg","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Pfanne","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Just","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Neum\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hegermann","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8444-0940","authenticated-orcid":false,"given":"Andreas","family":"Pich","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Core Unit Proteomics, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4518-6323","authenticated-orcid":false,"given":"Ante","family":"Radocaj","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Physiology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-1511","authenticated-orcid":false,"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1161\/CIRCRESAHA.113.302095","article-title":"Cardiac Metabolism and Its Interactions With Contraction, Growth, and Survival of Cardiomyocytes","volume":"113","author":"Kolwicz","year":"2013","journal-title":"Circ. 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