Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo
de Haan, Willeke × Out, Ruud Berbée, Jimmy F P van der Hoogt, Caroline C van Dijk, Ko Willems van Berkel, Theo J C Romijn, Johannes A Jukema, J Wouter Havekes, Louis M Rensen, Patrick C N #
Biochemical and Biophysical Research Communications vol:377 issue:4 pages:1294-8
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.