Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo

• Published in: Biochemical and biophysical research communications 2008-12, Vol.377 (4), p.1294-1298
• Main Authors: de Haan, Willeke, Out, Ruud, Berbée, Jimmy F.P., van der Hoogt, Caroline C., Dijk, Ko Willems van, van Berkel, Theo J.C., Romijn, Johannes A., Wouter Jukema, J., Havekes, Louis M., Rensen, Patrick C.N.
• Format: Article
• Language: English
• Subjects: Adenoviridae; Animals; ApoCI; Apolipoprotein C-I - genetics; Apolipoprotein C-I - pharmacology; Apolipoprotein C-I - physiology; Cholesterol, HDL - blood; Cholesterol, HDL - metabolism; Gene Transfer Techniques; Hepatocyte; Hepatocytes - drug effects; Hepatocytes - metabolism; High density lipoprotein; Humans; Mice; Mice, Knockout; Oxidized LDL; Scavenger Receptors, Class B - antagonists & inhibitors; SR-BI; Transgenic mice
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.10.147

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 [3H]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.