Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo.
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.
de Haan
Willeke
W
Dept. of General Internal Medicine, Leiden University Medical Center, P.O. Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
Out
Ruud
R
Berbée
Jimmy F P
JF
van der Hoogt
Caroline C
CC
van Dijk
Ko Willems
KW
van Berkel
Theo J C
TJ
Romijn
Johannes A
JA
Jukema
J Wouter
JW
Havekes
Louis M
LM
Rensen
Patrick C N
PC
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*
D053302:Apolipoprotein C-I; D008076:Cholesterol, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B