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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1912.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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; Kerry-Anne Rye; John L. Taylor; P. Hugh R. Barrett; Philip J. Barter

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.

Correspondence to Prof Philip J. Barter, Cardiovascular Investigation Unit, Level 6, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia. 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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