title: Prebeta high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice.
abstract: We compared the in vivo metabolism of prebeta HDL particles isolated by anti-human apolipoprotein A-I (apoA-I) immunoaffinity chromatography (LpA-I) in human apoA-I transgenic (hA-I Tg) mice with that of lipid-free apoA-I (LFA-I) and small LpA-I. After injection, prebeta LpA-I were removed from plasma more rapidly than were LFA-I and small LpA-I. Prebeta LpA-I and LFA-I were preferentially degraded by kidney compared with liver; small LpA-I were preferentially degraded by the liver. Five minutes after tracer injection, 99% of LFA-I in plasma was found to be associated with medium-sized (8.6 nm) HDL, whereas only 37% of prebeta tracer remodeled to medium-sized HDL. Injection of prebeta LpA-I doses into C57Bl/6 recipients resulted in a slower plasma decay compared with hA-I Tg recipients and a greater proportion (>60%) of the prebeta radiolabel that was associated with medium-sized HDL. Prebeta LpA-I contained one to four molecules of phosphatidylcholine per molecule of apoA-I, whereas LFA-I contained less than one. We conclude that prebeta LpA-I has two metabolic fates in vivo, rapid removal from plasma and catabolism by kidney or remodeling to medium-sized HDL, which we hypothesize is determined by the amount of lipid associated with the prebeta particle and the particle's ability to bind to medium-sized HDL.
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Lorraine
authors.initials: L
authors.lastname: Lanningham-Foster
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Boudyguina
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Smith
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Young
authors.forename: Perry L
authors.initials: PL
authors.lastname: Colvin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thomas
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010316:Particle Size; D010743:Phospholipids / Q000032:analysis; D011485:Protein Binding
chemical_list: D016632:Apolipoprotein A-I; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D010743:Phospholipids