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Because LDL particles contain less cholesterol on statin therapy, the delivery of cholesterol to the liver must, therefore, be reduced. PCSK9 inhibitors reduce the production of LDL particles and this further reduces cholesterol delivery to the liver. With both agents, a larger fraction of a smaller pool is removed per unit time. These findings are inconsistent with the conventional model of cholesterol homeostasis within the liver, but are consistent with a new model of regulation, the multi-channel model, which postulates that different lipoprotein particles enter the hepatocyte by different routes and have different metabolic fates within the hepatocyte. The multi-channel model, but not the conventional model, may explain how statins and PCSK9 inhibitors can produce sustained increases in LDL receptor number.<\/jats:p>","DOI":"10.1042\/cs20160872","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:20:22Z","timestamp":1492647622000},"page":"791-797","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Statins, PCSK9 inhibitors and cholesterol homeostasis: a view from within the hepatocyte"],"prefix":"10.1042","volume":"131","author":[{"given":"Allan\u00a0D.","family":"Sniderman","sequence":"first","affiliation":[{"name":"Royal Victoria Hospital\u2013McGill University Health Centre 1001, Decarie Boul., Montreal, Quebec, Canada H4A 3J1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert\u00a0Scott","family":"Kiss","sequence":"additional","affiliation":[{"name":"Royal Victoria Hospital\u2013McGill University Health Centre 1001, Decarie Boul., Montreal, Quebec, Canada H4A 3J1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Reid","sequence":"additional","affiliation":[{"name":"Royal Victoria Hospital\u2013McGill University Health Centre 1001, Decarie Boul., Montreal, Quebec, Canada H4A 3J1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Thanassoulis","sequence":"additional","affiliation":[{"name":"Royal Victoria Hospital\u2013McGill University Health Centre 1001, Decarie Boul., Montreal, Quebec, Canada H4A 3J1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald\u00a0F.","family":"Watts","sequence":"additional","affiliation":[{"name":"Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine, University of Western Australia, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2017,4,19]]},"reference":[{"key":"2021113010555580700_B1","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.2119\/molmed.2014.00194","article-title":"Statins: definitive translational research","volume":"20","author":"Grundy","year":"2014","journal-title":"Mol. 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