title: ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT.
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.
authors.affiliation: Molecular Genetics, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Adelina
authors.initials: A
authors.lastname: Duka
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Fotakis
authors.forename: Dimitra
authors.initials: D
authors.lastname: Georgiadou
authors.forename: Andreas
authors.initials: A
authors.lastname: Kateifides
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Tzavlaki
authors.forename: Leonard
authors.initials: L
authors.lastname: von Eckardstein
authors.forename: Efstratios
authors.initials: E
authors.lastname: Stratikos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kardassis
authors.forename: Vassilis I
authors.initials: VI
authors.lastname: Zannis
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000737:chemistry*; D051379:Mice; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase