{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:04:50Z","timestamp":1789718690504,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatohepatitis (MASH) is increasingly linked to cardiovascular complications; however, the mechanisms underlying the association between hepatic injury and cardiotoxicity remain unclear. This study aimed to establish a wild\u2010type mouse model of MASH with cardiac involvement and to characterise the temporal relationship between hepatic and cardiac alterations during disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male C57BL\/6J mice were fed a standard diet or a low\u2010carbohydrate, high\u2010protein, high\u2010cholesterol (LCHP\u2010HC) diet with or without non\u2010excessive ethanol for 12 or 24\u2009weeks. Arrhythmogenic susceptibility was assessed using provocation testing. Hepatic and cardiac alterations were evaluated by histology, immunofluorescence, and quantitative RT\u2010PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The LCHP\u2010HC diet combined with ethanol induced histological MASH and markedly increased susceptibility to lethal arrhythmias. At 12\u2009weeks, cardiac remodelling characterised by inflammation, mild fibrosis, and connexin\u201043 dysregulation was evident in the absence of hepatic fibrosis, indicating early cardiotoxic remodelling. At 24\u2009weeks, hepatic fibrosis and hepatic sympathetic activation became evident, whereas local cardiac sympathetic activation remained unchanged, indicating a temporal dissociation in which cardiac remodelling preceded hepatic fibrotic progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Early cardiotoxic remodelling preceded hepatic fibrosis and was associated with increased arrhythmogenic susceptibility during MASH progression. These findings demonstrate that cardiac remodelling develops early in experimental MASH and reveal a stage\u2010dependent temporal association between hepatic disease progression and cardiac vulnerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70154","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:37:29Z","timestamp":1787719049000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Cardiotoxic Remodelling Precedes Hepatic Fibrosis and Increases Susceptibility to Lethal Arrhythmias in Wild\u2010Type\n                    <scp>MASH<\/scp>\n                    Mice"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3857-5259","authenticated-orcid":false,"given":"Jinyao","family":"Liu","sequence":"first","affiliation":[{"name":"Student Medical Academia Investigation Lab Yamaguchi University Graduate School of Medicine  Ube Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohmei","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Student Medical Academia Investigation Lab Yamaguchi University Graduate School of Medicine  Ube Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiko","family":"Yamano","sequence":"additional","affiliation":[{"name":"Life Science Division Yamaguchi University Advanced Technology Institute  Ube Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-025-03151-9"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.70053"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2025.100806"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.3567"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-02070-5"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e34915"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22363"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.70335"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacadv.2024.100924"},{"issue":"2","key":"e_1_2_13_12_1","first-page":"5","article-title":"Use of Low\u2010Carbohydrate, High\u2010Protein Diets Among Americans: Correlates, Duration, and Weight Loss","volume":"8","author":"Blanck H. 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