Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL*s⃞

We investigated the in vivo metabolic fate of pre-β HDL particles in human apolipoprotein A-I transgenic (hA-ITg) mice. Pre-β HDL tracers were assembled by incubation of [125I]tyramine cellobiose-labeled apolipoprotein A-I (apoA-I) with HEK293 cells expressing ABCA1. Radiolabeled pre-β HDLs of increasing size (pre-β1, -2, -3, and -4 HDLs) were isolated by fast-protein liquid chromatography and injected into hA-ITg-recipient mice, after which plasma decay, in vivo remodeling, and tissue uptake were monitored. Pre-β2, -3, and -4 had similar plasma die-away rates, whereas pre-β1 HDL was removed 7-fold more rapidly. Radiolabel recovered in liver and kidney 24 h after tracer injection suggested increased (P < 0.001) liver and decreased kidney catabolism as pre-β HDL size increased. In plasma, pre-β1 and -2 were rapidly (