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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300422-JLR200 on January 16, 2004

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Journal of Lipid Research, Vol. 45, 716-728, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Preß high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice

Ji-Young Lee*, Lorraine Lanningham-Foster*, Elena Y. Boudyguina*, Thomas L. Smith{dagger}, Ellen R. Young*, Perry L. Colvin§, Michael J. Thomas** and John S. Parks1,*

* Departments of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
{dagger} Orthopedic Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27157
** Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157
§ Division of Gerontology, University of Maryland School of Medicine, and Geriatrics Research, Education, and Clinical Center, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201

1 To whom correspondence should be addressed. e-mail: jparks{at}wfubmc.edu

We compared the in vivo metabolism of preß 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, preß LpA-I were removed from plasma more rapidly than were LFA-I and small LpA-I. Preß 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 preß tracer remodeled to medium-sized HDL. Injection of preß 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 preß radiolabel that was associated with medium-sized HDL. Preß LpA-I contained one to four molecules of phosphatidylcholine per molecule of apoA-I, whereas LFA-I contained less than one.

We conclude that preß 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 preß particle and the particle's ability to bind to medium-sized HDL.

Abbreviations: apoA-I, apolipoprotein A-I; CETP, cholesteryl ester transfer protein; FCR, fractional catabolic rate; FPLC, fast-protein liquid chromatography; hA-I Tg, human apolipoprotein A-I transgenic; HL, hepatic lipase; LFA-I, lipid-free apolipoprotein A-I; LpA-I, HDL particles isolated by anti-human apolipoprotein A-I immunoaffinity chromatography; PC, phosphatidylcholine; PLTP, phospholipid transfer protein; RCT, reverse cholesterol transport; TC, tyramine cellobiose

Supplementary key words high density lipoprotein metabolism • in vivo • lipid-free apolipoprotein A-I • fractional catabolic rate • turnover • die-away • immunoaffinity chromatography • high density lipoprotein subfractions


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