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Journal of Lipid Research, Vol. 47, 115-122, January 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Formation of high density lipoproteins containing both apolipoprotein A-I and A-II in the rabbit

Neil J. Hime^1,*, Kate J. Drew^*, Kevin Wee^*, Philip J. Barter^*, and Kerry-Anne Rye^2,*,,

^* Lipid Research Group, The Heart Research Institute, Camperdown, Sydney, New South Wales 2050, Australia
Department of Medicine, University of Sydney, New South Wales 2006, Australia
Department of Medicine, University of Melbourne, Victoria 3010, Australia

Published, JLR Papers in Press, October 12, 2005.

¹ Present address of N. J. Hime: The Scripps Research Institute, Immunology Department, North Torrey Pines Road, La Jolla, CA 92037.

² To whom correspondence should be addressed. e-mail: k.rye{at}hri.org.au

Human plasma HDLs are classified on the basis of apolipoprotein composition into those that contain apolipoprotein A-I (apoA-I) without apoA-II [(A-I)HDL] and those containing apoA-I and apoA-II [(A-I/A-II)HDL]. ApoA-I enters the plasma as a component of discoidal particles, which are remodeled into spherical (A-I)HDL by LCAT. ApoA-II is secreted into the plasma either in the lipid-free form or as a component of discoidal high density lipoproteins containing apoA-II without apoA-I [(A-II)HDL]. As discoidal (A-II)HDL are poor substrates for LCAT, they are not converted into spherical (A-II)HDL. This study investigates the fate of apoA-II when it enters the plasma. Lipid-free apoA-II and apoA-II-containing discoidal reconstituted HDL [(A-II)rHDL] were injected intravenously into New Zealand White rabbits, a species that is deficient in apoA-II. In both cases, the apoA-II was rapidly and quantitatively incorporated into spherical (A-I)HDL to form spherical (A-I/A-II)HDL. These particles were comparable in size and composition to the (A-I/A-II)HDL in human plasma. Injection of lipid-free apoA-II and discoidal (A-II)rHDL was also accompanied by triglyceride enrichment of the endogenous (A-I)HDL and VLDL as well as the newly formed (A-I/A-II)HDL. We conclude that, irrespective of the form in which apoA-II enters the plasma, it is rapidly incorporated into spherical HDLs that also contain apoA-I to form (A-I/A-II)HDL.

Supplementary key words high density lipoproteins containing apolipoprotein A-I without apolipoprotein A-II • high density lipoprotein formation • triglyceride-enriched high density lipoproteins

Abbreviations: apoA-I, apolipoprotein A-I; (A-I)HDL, high density lipoproteins containing apolipoprotein A-I without apolipoprotein A-II; (A-I/A-II)HDL, high density lipoproteins containing apolipoprotein A-I and apolipoprotein A-II; (A-II)HDL, high density lipoproteins containing apolipoprotein A-II without apolipoprotein A-I; rHDL, reconstituted high density lipoprotein

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