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.

OBJECTIVE Apolipoprotein (apo)A-I exists in 3 forms in plasma: as lipid-free apoA-I, as a component of pre-beta-migrating discoidal high density lipoproteins (HDLs), and as a component of alpha-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 (125)I-apoA-I and 125I-apoA-I in pre-beta-migrating discoidal reconstituted HDLs (rHDLs) were injected into wild-type rabbits, the label rapidly appeared in alpha-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 alpha-migrating particles, (2) pre-beta-migrating discoidal HDLs are rapidly converted into alpha-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 alpha-migrating HDLs and increases the rate of catabolism of apoA-I.