title: Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo.
abstract: Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of apoCI on the SR-BI-mediated uptake of HDL-CE in vitro and determined the net effect of apoCI on HDL metabolism in mice. Enrichment of HDL with apoCI dose-dependently decreased the SR-BI-dependent association of [(3)H]CE-labeled HDL with primary murine hepatocytes, similar to the established SR-BI-inhibitors apoCIII and oxLDL. ApoCI deficiency in mice gene dose-dependently decreased HDL-cholesterol levels. Adenovirus-mediated expression of human apoCI in mice increased HDL levels at a low dose and increased the HDL particle size at higher doses. We conclude that apoCI is a novel inhibitor of SR-BI in vitro and increases HDL levels in vivo.
authors.affiliation: Dept. of General Internal Medicine, Leiden University Medical Center, P.O. Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
authors.forename: Willeke
authors.initials: W
authors.lastname: de Haan
authors.forename: Ruud
authors.initials: R
authors.lastname: Out
authors.forename: Jimmy F P
authors.initials: JF
authors.lastname: Berbée
authors.forename: Caroline C
authors.initials: CC
authors.lastname: van der Hoogt
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
mesh_terms: D000256:Adenoviridae; D000818:Animals; D053302:Apolipoprotein C-I / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D008076:Cholesterol, HDL / Q000097:blood* / Q000378:metabolism; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors*
chemical_list: D053302:Apolipoprotein C-I; D008076:Cholesterol, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B