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This was mechanistically explained by an inhibition of de novo lipogenesis in the liver, increased synthesis of bile acids from cholesterol, and down-regulated apolipoprotein B synthesis, which resulted in decreased cholesterol secretion in very low\u2013density lipoprotein particles. As a consequence, IC7Fc treatment considerably reduced atherosclerotic lesion formation and vascular inflammation compared with current antihyperlipidemic therapy. In conclusion, IC7Fc is a promising pharmacological treatment for cardiometabolic diseases targeting hyperlipidemia and inflammation.<\/jats:p>","DOI":"10.1126\/sciadv.adx3794","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:58:36Z","timestamp":1761328716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["The designer cytokine IC7Fc attenuates atherosclerosis development by targeting hyperlipidemia in mice"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4394-6387","authenticated-orcid":true,"given":"Wietse","family":"In het Panhuis","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands."},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands."},{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands."},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1145-2344","authenticated-orcid":true,"given":"Ellen","family":"Thiemann","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands."},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2531-2292","authenticated-orcid":true,"given":"Daisy M. 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