on September 26, 2002
Published online before print September 26, 2002, doi: 10.1161/01.ATV.0000038485.94020.7F
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Submitted on August 14, 2002
Accepted on September 4, 2002
Metabolism of ApoA-I as Lipid-Free Protein or as Component of Discoidal and Spherical Reconstituted HDLs. Studies in Wild-Type and Hepatic Lipase Transgenic Rabbits
Patrick Kee ;
From the University Department of Medicine (P.K., P.J.B.), Royal Adelaide Hospital, and the Lipid Research Laboratory (P.K., K.-A.R., P.J.B.), Hanson Institute, Adelaide, Australia; the Gladstone Institute of Cardiovascular Disease (J.L.T.), University of California, San Francisco; and the Department of Medicine (P.H.R.B.), University of Western Australia and the Western Australian Institute for Medical Research, Perth, Australia.
* To whom correspondence should be addressed. E-mail: philip.barter{at}adelaide.edu.au.
Objective—Apolipoprotein (apo)A-I exists in 3 forms in plasma: as lipid-free apoA-I, as a component of pre-ß-migrating discoidal high density lipoproteins (HDLs), and as a component of 
-migrating spherical HDLs. This study investigates (1) the in vivo metabolism of apoA-I in each of these forms and (2) the effects of hepatic lipase (HL) on apoA-I metabolism.
Methods and Results—Wild-type and HL transgenic rabbits were studied. When lipid-free 125I-apoA-I and 125I-apoA-I in pre-ß-migrating discoidal reconstituted HDLs (rHDLs) were injected into wild-type rabbits, the label rapidly appeared in -migrating particles and decayed with the same fractional catabolic rate (FCR) as when they were injected as a component of spherical rHDLs. Spherical rHDLs did not change in size when they were injected into wild-type rabbits but were reduced in size in HL transgenic rabbits. The FCR of apoA-I in HL transgenic rabbits was double that in wild-type rabbits.
Conclusions—In vivo, (1) lipid-free apoA-I rapidly incorporates into preexisting -migrating particles, (2) pre-ß-migrating discoidal HDLs are rapidly converted into -migrating HDLs, (3) the FCR of apoA-I is independent of the form in which it is introduced into plasma, and (4) HL reduces the size of -migrating HDLs and increases the rate of catabolism of apoA-I.
Key words: apolipoprotein A-I • hepatic lipase • high density lipoproteins • metabolism • rabbits
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