{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:01Z","timestamp":1791920101571,"version":"4.3.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"40","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Austrian Science Fund","award":["TRP-188"],"award-info":[{"award-number":["TRP-188"]}]},{"name":"Doctoral program HOROS","award":["W-1253"],"award-info":[{"award-number":["W-1253"]}]},{"name":"Christian Doppler Society"},{"name":"Medical University Innsbruck for young scientists MUI-START","award":["2017-01-011"],"award-info":[{"award-number":["2017-01-011"]}]},{"name":"COMET project VASCage Tyrol [K-Project","award":["843536"],"award-info":[{"award-number":["843536"]}]},{"name":"Austrian Research Promotion Agency FFG"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["33CS30-148470\/1&2"],"award-info":[{"award-number":["33CS30-148470\/1&2"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Imbalances of iron metabolism have been linked to the development of atherosclerosis. However, subjects with hereditary haemochromatosis have a lower prevalence of cardiovascular disease. The aim of our study was to understand the underlying mechanisms by combining data from genome-wide association study analyses in humans, CRISPR\/Cas9 genome editing, and loss-of-function studies in mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Our analysis of the Global Lipids Genetics Consortium (GLGC) dataset revealed that single nucleotide polymorphisms (SNPs) in the haemochromatosis gene HFE associate with reduced low-density lipoprotein cholesterol (LDL-C) in human plasma. The LDL-C lowering effect could be phenocopied in dyslipidaemic ApoE\u2212\/\u2212 mice lacking Hfe, which translated into reduced atherosclerosis burden. Mechanistically, we identified HFE as a negative regulator of LDL receptor expression in hepatocytes. Moreover, we uncovered liver-resident Kupffer cells (KCs) as central players in cholesterol homeostasis as they were found to acquire and transfer LDL-derived cholesterol to hepatocytes in an Abca1-dependent fashion, which is controlled by iron availability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results disentangle novel regulatory interactions between iron metabolism, KC biology and cholesterol homeostasis which are promising targets for treating dyslipidaemia but also provide a mechanistic explanation for reduced cardiovascular morbidity in subjects with haemochromatosis.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaa140","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T12:16:07Z","timestamp":1582028167000},"page":"3949-3959","source":"Crossref","is-referenced-by-count":49,"title":["The haemochromatosis gene Hfe and Kupffer cells control LDL cholesterol homeostasis and impact on atherosclerosis development"],"prefix":"10.1093","volume":"41","author":[{"given":"Egon","family":"Demetz","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstra\u00dfe 35 , 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0398-6034","authenticated-orcid":false,"given":"Piotr","family":"Tymoszuk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstra\u00dfe 35 , 6020 Innsbruck, 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