{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:53:25Z","timestamp":1762300405646,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Amiodarone is an effective antiarrhythmic drug, which interferes with cholesterol synthesis. In the human body, it inhibits two enzymes in the cholesterol\u2010synthesis pathway, followed by increases especially in serum desmosterol and zymostenol concentrations and a decrease in that of serum lathosterol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We explored whether desmosterol and zymostenol accumulate also in myocardial tissue during amiodarone treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010three patients admitted for cardiac transplantation volunteered for the study. Ten patients were on amiodarone treatment (AD group) and 23 were not (control group). The groups were matched as regards demographic and clinical variables. Myocardial samples were obtained from the removed hearts from 31 patients. Cholesterol, non\u2010cholesterol sterols and squalene were quantified by means of gas\u2013liquid chromatography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In serum and myocardium, desmosterol was 19\u2010 and 18\u2010fold higher and zymostenol 4\u2010 and 2\u2010fold higher in the AD group versus the control group (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001 for all). In contrast, myocardial cholesterol, squalene and lathosterol levels were lower in the AD group than in the control group (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05 for all). Levels of phytosterols and cholestanol were similar in the serum and myocardium in the two groups. Levels of myocardial and serum desmosterol, zymostenol, lathosterol and phytosterols correlated with each other in both groups (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05 for all).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Amiodarone treatment caused the accumulation of desmosterol and zymostenol in myocardium. In particular, myocardial desmosterol concentrations were substantially elevated, which may play a part in some of the therapeutic and adverse effects of amiodarone treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13693","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T04:40:10Z","timestamp":1688445610000},"page":"506-514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Amiodarone accumulates two cholesterol precursors in myocardium: A controlled clinical study"],"prefix":"10.1111","volume":"294","author":[{"given":"Piia","family":"Simonen","sequence":"first","affiliation":[{"name":"Heart and Lung Center, Cardiology University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyri","family":"Lommi","sequence":"additional","affiliation":[{"name":"Heart and Lung Center, Cardiology University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Lemstr\u00f6m","sequence":"additional","affiliation":[{"name":"Heart and Lung Center University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Tolva","sequence":"additional","affiliation":[{"name":"Transplantation Laboratory Department of Pathology University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juha","family":"Sinisalo","sequence":"additional","affiliation":[{"name":"Heart and Lung Center, Cardiology University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-8367","authenticated-orcid":false,"given":"Helena","family":"Gylling","sequence":"additional","affiliation":[{"name":"Heart and Lung Center University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct065916"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2015.08.039"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005344"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.107047"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.72.5.1064"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.07.090"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12682"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13095"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00042"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.3.591"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980113)75:2<145::AID-AJMG5>3.0.CO;2-S"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/323473"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.10873"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34040"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.74"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509530200"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38566-7"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(89)90252-7"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115479"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.08.003"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37014-0"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV120.010723"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.01.015"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-94"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.11.009"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603781200"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2107682118"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.054"}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13693","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T06:24:34Z","timestamp":1695018274000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joim.13693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,6]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1111\/joim.13693"],"URL":"https:\/\/doi.org\/10.1111\/joim.13693","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"type":"print","value":"0954-6820"},{"type":"electronic","value":"1365-2796"}],"subject":[],"published":{"date-parts":[[2023,7,6]]},"assertion":[{"value":"2023-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}