ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT |
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Authors: | Adelina Duka Panagiotis Fotakis Dimitra Georgiadou Andreas Kateifides Kalliopi Tzavlaki Leonard von Eckardstein Efstratios Stratikos Dimitris Kardassis Vassilis I Zannis |
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Institution: | *Molecular Genetics, Boston University School of Medicine, Boston, MA;†National Centre for Scientific Research “Demokritos,” Athens, Greece;§Department of Biochemistry, University of Crete Medical School, Heraklion, Greece |
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Abstract: | The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse models. Adenovirus-mediated gene transfer of apoA-IV in apoA-I−/− mice did not change plasma lipid levels. ApoA-IV floated in the HDL2/HDL3 region, promoted the formation of spherical HDL particles as determined by electron microscopy, and generated mostly α- and a few pre-β-like HDL subpopulations. Gene transfer of apoA-IV in apoA-I−/− × apoE−/− mice increased plasma cholesterol and triglyceride levels, and 80% of the protein was distributed in the VLDL/IDL/LDL region. This treatment likewise generated α- and pre-β-like HDL subpopulations. Spherical and α-migrating HDL particles were not detectable following gene transfer of apoA-IV in ABCA1−/− or LCAT−/− mice. Coexpression of apoA-IV and LCAT in apoA-I−/− mice restored the formation of HDL-A-IV. Lipid-free apoA-IV and reconstituted HDL-A-IV promoted ABCA1 and scavenger receptor BI (SR-BI)-mediated cholesterol efflux, respectively, as efficiently as apoA-I and apoE. Our findings are consistent with a novel function of apoA-IV in the biogenesis of discrete HDL-A-IV particles with the participation of ABCA1 and LCAT, and may explain previously reported anti-inflammatory and atheroprotective properties of apoA-IV. |
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Keywords: | apolipoprotein A-IV lipoproteins genetically altered mice lecithin:cholesterol acyltransferase ATP binding cassette transporter A1 |
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