PXR agonism decreases plasma HDL levels in ApoE*3-Leiden.CETP mice
| Autor: | Haan, W. de, Vries-van der Weij, J. de, Mol, I.M., Hoekstra, M., Romijn, J.A., Jukema, J.W., Havekes, L.M., Princen, H.M.G., Rensen, P.C.N. |
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| Přispěvatelé: | TNO Kwaliteit van Leven |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Pregnenolone Carbonitrile
Receptors Steroid Biomedical Research High density lipoprotein cholesterol blood level Apolipoprotein E3 complementary DNA pregnane X receptor Mice 5 pregnen 3beta ol 20 one 16alpha carbonitrile cholesterol ester transfer protein Transgenic mice lipoprotein metabolism messenger RNA tritium ABC transporter A1 Mus article Scavenger Receptors Class B Cholesteryl ester transfer protein Lipids unclassified drug female priority journal Liver pregnenolone derivative lipids (amino acids peptides and proteins) cholesterol oleate triacylglycerol Lipoproteins animal experiment Immunoblotting lipid liver level Mice Transgenic animal tissue reverse transcription polymerase chain reaction Animals Mus musculus controlled study RNA Messenger Biology Triglycerides mouse plasma nonhuman Cholesterol HDL cholesterol triacylglycerol blood level Cholesterol Ester Transfer Proteins transgenic mouse gene expression ATP-Binding Cassette Transporters atherosclerosis low density lipoprotein polyacrylamide gel electrophoresis |
| Zdroj: | Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 3, 1791, 191-197 |
| Popis: | Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for human-like lipoprotein metabolism. Female mice were fed a diet with increasing amounts of the potent PXR agonist 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN). In E3L and E3L.CETP mice, PCN increased liver lipids as well as plasma cholesterol and triglycerides. However, whereas PCN increased cholesterol contained in large HDL-1 particles in E3L mice, it dose-dependently decreased HDL-cholesterol in E3L.CETP mice, indicating that CETP expression dominates the effect of PCN on HDL metabolism. Analysis of the hepatic expression of genes involved in HDL metabolism showed that PCN decreased expression of genes involved in HDL synthesis (Abca1, Apoa1), maturation (Lcat, Pltp) and clearance (Sr-b1). The HDL-increasing effect of PCN, observed in E3L mice, is likely caused by a marked decrease in hepatic SR-BI protein expression, and completely reversed by CETP expression. We conclude that chronic PXR agonism dose-dependently reduces plasma HDL-cholesterol in the presence of CETP. © 2008 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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