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A more recent version of this article appeared on January 1, 2006

Papers In Press, published online ahead of print October 12, 2005
J. Lipid Res., doi:10.1194/jlr.M500284-JLR200
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Submitted on July 6, 2005
Revised on September 29, 2005
Accepted on October 11, 2005

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

Neil J. Hime, Kate J. Drew, Kevin Wee, Philip J. Barter, and Kerry Anne Rye

Lipid Research Group, The Heart Research Institute, Camperdown, New South Wales 2050

Corresponding Author: karye{at}ozemail.com.au

The HDL in human plasma 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 is synthesized in the liver and intestine, and secreted into the plasma as discoidal particles complexed with phospholipids. Discoidal (A-I)HDL are remodelled into spherical (A-I)HDL by LCAT. ApoA-II is synthesized in the liver, and is probably also secreted into the plasma as a component of discoidal HDL. As discoidal HDL that contain apoA-II, (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 that enters the plasma in either the lipid-free form or as a component of discoidal (A-II)HDL. 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 naturally deficient in apoA-II, and does not have endogenous (A-I/A-II)HDL. In both cases the apoA-II was rapidly and quantitatively incorporated into spherical HDL that also contained apoA-I to form spherical (A-I/A-II)HDL. These particles were comparable in size and composition to the spherical (A-I/A-II)HDL in human plasma. Injection of lipid-free apoA-II and discoidal (A-II)rHDL into rabbits also resulted in triglyceride-enrichment of the endogenous (A-I)HDL and VLDL, as well as the newly formed (A-I/A-II)HDL. It is concluded that, irrespective of whether apoA-II enters the plasma in the lipid-free form or as a component of discoidal (A-II)rHDL, it is rapidly incorporated into spherical HDL that also contain apoA-I to form (A-I/A-II)HDL.


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