Author:

Keywords:

Adenoviridae, Animals, Apolipoprotein C-I, Cholesterol, HDL, Gene Transfer Techniques, Hepatocytes, Humans, Mice, Mice, Knockout, Scavenger Receptors, Class B, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, ApoCl, Hepatocyte, High density lipoprotein, Oxidized LDL, SR-BI, Transgenic mice, DENSITY-LIPOPROTEIN RECEPTOR, ESTER TRANSFER PROTEIN, LECITHIN-CHOLESTEROL ACYLTRANSFERASE, TRANSGENIC MICE, HEPATIC LIPASE, APOC-I, SEVERE HYPERTRIGLYCERIDEMIA, SELECTIVE UPTAKE, METABOLISM, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry

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.