title: Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile.
abstract: The clearance of free cholesterol from plasma lipoproteins by tissues is of major quantitative importance, but it is not known whether this is passive or receptor-mediated. Based on our finding that scavenger receptor BI (SR-BI) promotes free cholesterol (FC) exchange between high density lipoprotein (HDL) and cells, we tested whether SR-BI would effect FC movement in vivo using [(14)C]FC- and [(3)H]cholesteryl ester (CE)-labeled HDL in mice with increased (SR-BI transgenic (Tg)) or decreased (SR-BI attenuated (att)) hepatic SR-BI expression. The initial clearance of HDL FC was increased in SR-BI Tg mice by 72% and decreased in SR-BI att mice by 53%, but was unchanged in apoA-I knockout mice compared with wild-type mice. Transfer of FC to non-HDL and esterification of FC were minor and could not explain differences. The hepatic uptake of FC was increased in SR-BI Tg mice by 34% and decreased in SR-BI att mice by 22%. CE clearance and uptake gave similar results, but with much slower rates. The uptake of HDL FC and CE by SR-BI Tg primary hepatocytes was increased by 2.2- and 2.6-fold (1-h incubation), respectively, compared with control hepatocytes. In SR-BI Tg mice, the initial biliary secretion of [(14)C]FC was markedly increased, whereas increased [(3)H]FC appeared after a slight delay. Thus, in the mouse, a major portion of the clearance of HDL FC from plasma is mediated by SR-BI.
authors.affiliation: Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: E
authors.initials: E
authors.lastname: Sehayek
authors.forename: D
authors.initials: D
authors.lastname: Huszar
authors.forename: J L
authors.initials: JL
authors.lastname: Breslow
authors.forename: A R
authors.initials: AR
authors.lastname: Tall
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
chemical_list: D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B