Hong Mao, Larissa D. Kruse, Ruomei Li, Ana Oteiza, Eike C. Struck, Jasmin Schürstedt, Wolfgang Hübner, Victoria C. Cogger, David Le Couteur, Deanna L. Wolfson, Thomas Huser, Balpreet Singh Ahluwalia, Cristina Øie, Peter A. G. McCourt
{"title":"氧化低密度脂蛋白对大鼠肝窦内皮细胞形态和功能的影响","authors":"Hong Mao, Larissa D. Kruse, Ruomei Li, Ana Oteiza, Eike C. Struck, Jasmin Schürstedt, Wolfgang Hübner, Victoria C. Cogger, David Le Couteur, Deanna L. Wolfson, Thomas Huser, Balpreet Singh Ahluwalia, Cristina Øie, Peter A. G. McCourt","doi":"10.1038/s44355-024-00009-5","DOIUrl":null,"url":null,"abstract":"Atherogenesis is associated with elevated plasma levels of oxidized low-density lipoproteins (oxLDL). In vivo, oxLDL causes liver endothelial swelling, and disrupts liver sinusoidal endothelial cell (LSECs) fenestrations. We mapped the nanoscale kinetics of these changes in vitro in isolated rat LSECs challenged with oxLDL and monitored viability with endocytosis and cytotoxicity assays. OxLDL disrupted LSEC ultrastructure – increasing oxLDL concentrations and oxidation levels caused sieve plate loss, fenestration fusion, and gap formation. Importantly, these effects were not uniform across all LSECs. LSECs retained the ability to endocytose ligands irrespective of the presence of oxLDL. However, increasing oxidation levels and concentrations of oxLDL inhibited LSEC mediated degradation of endocytosed ligands. Viability was unaffected by any oxLDL challenge. In conclusion, oxLDL disrupts LSEC ultrastructural morphology in vitro but LSECs remain viable and mostly maintain the scavenging function during oxLDL challenge.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-11"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00009-5.pdf","citationCount":"0","resultStr":"{\"title\":\"Impact of oxidized low-density lipoprotein on rat liver sinusoidal endothelial cell morphology and function\",\"authors\":\"Hong Mao, Larissa D. Kruse, Ruomei Li, Ana Oteiza, Eike C. Struck, Jasmin Schürstedt, Wolfgang Hübner, Victoria C. Cogger, David Le Couteur, Deanna L. Wolfson, Thomas Huser, Balpreet Singh Ahluwalia, Cristina Øie, Peter A. G. McCourt\",\"doi\":\"10.1038/s44355-024-00009-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Atherogenesis is associated with elevated plasma levels of oxidized low-density lipoproteins (oxLDL). In vivo, oxLDL causes liver endothelial swelling, and disrupts liver sinusoidal endothelial cell (LSECs) fenestrations. We mapped the nanoscale kinetics of these changes in vitro in isolated rat LSECs challenged with oxLDL and monitored viability with endocytosis and cytotoxicity assays. OxLDL disrupted LSEC ultrastructure – increasing oxLDL concentrations and oxidation levels caused sieve plate loss, fenestration fusion, and gap formation. Importantly, these effects were not uniform across all LSECs. LSECs retained the ability to endocytose ligands irrespective of the presence of oxLDL. However, increasing oxidation levels and concentrations of oxLDL inhibited LSEC mediated degradation of endocytosed ligands. Viability was unaffected by any oxLDL challenge. In conclusion, oxLDL disrupts LSEC ultrastructural morphology in vitro but LSECs remain viable and mostly maintain the scavenging function during oxLDL challenge.\",\"PeriodicalId\":501708,\"journal\":{\"name\":\"npj Gut and Liver\",\"volume\":\" \",\"pages\":\"1-11\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s44355-024-00009-5.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Gut and Liver\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.nature.com/articles/s44355-024-00009-5\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Gut and Liver","FirstCategoryId":"1085","ListUrlMain":"https://www.nature.com/articles/s44355-024-00009-5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Impact of oxidized low-density lipoprotein on rat liver sinusoidal endothelial cell morphology and function
Atherogenesis is associated with elevated plasma levels of oxidized low-density lipoproteins (oxLDL). In vivo, oxLDL causes liver endothelial swelling, and disrupts liver sinusoidal endothelial cell (LSECs) fenestrations. We mapped the nanoscale kinetics of these changes in vitro in isolated rat LSECs challenged with oxLDL and monitored viability with endocytosis and cytotoxicity assays. OxLDL disrupted LSEC ultrastructure – increasing oxLDL concentrations and oxidation levels caused sieve plate loss, fenestration fusion, and gap formation. Importantly, these effects were not uniform across all LSECs. LSECs retained the ability to endocytose ligands irrespective of the presence of oxLDL. However, increasing oxidation levels and concentrations of oxLDL inhibited LSEC mediated degradation of endocytosed ligands. Viability was unaffected by any oxLDL challenge. In conclusion, oxLDL disrupts LSEC ultrastructural morphology in vitro but LSECs remain viable and mostly maintain the scavenging function during oxLDL challenge.