Prebeta high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice.
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.
Lee
Ji-Young
JY
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Lanningham-Foster
Lorraine
L
Boudyguina
Elena Y
EY
Smith
Thomas L
TL
Young
Ellen R
ER
Colvin
Perry L
PL
Thomas
Michael J
MJ
Parks
John S
JS
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
D016632:Apolipoprotein A-I; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D010743:Phospholipids