ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT

作者：Duka Adelina; Fotakis Panagiotis; Georgiadou Dimitra; Kateifides Andreas; Tzavlaki Kalliopi; von Eckardstein Leonard; Stratikos Efstratios; Kardassis Dimitris; Zannis Vassilis I^*

来源：The Journal of Lipid Research, 2013, 54(1): 107-115.

DOI：10.1194/jlr.M030114

• apolipoprotein A-IV
• lipoproteins
• genetically altered mice
• lecithin:cholesterol acyltransferase
• ATP binding cassette transporter A1

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 alpha- and a few pre-beta-like HDL subpopulations. Gene transfer of apoA-IV in apoA-I-/- x 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 alpha- and pre-beta-like HDL subpopulations. Spherical and alpha-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.-Duka, A., P. Fotakis, D. Georgiadou, A. Kateifides, K. Tzavlaki, L. von Eclardstein, E. Stratikos, D. Kardassis, and V. I. Zannis. ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT. J. Lipid Res. 2013. 54: 107-115.

• 出版日期2013-1