Date of this Version
Published, JLR Papers in Press, June 25, 2008. DOI 10.1194/jlr.M800241-JLR200
We investigated the in vivo metabolic fate of preb HDL particles in human apolipoprotein A-I transgenic (hA-I Tg) mice. Pre-b HDL tracers were assembled by incubation of [125I]tyramine cellobiose-labeled apolipoprotein A-I (apoA-I) with HEK293 cells expressing ABCA1. Radiolabeled pre-b HDLs of increasing size (pre-b1, -2, -3, and -4 HDLs) were isolated by fast-protein liquid chromatography and injected into hA-I Tg-recipient mice, after which plasma decay, in vivo remodeling, and tissue uptake were monitored. Pre-b2, -3, and -4 had similar plasma die-away rates, whereas pre-b1 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-b HDL size increased. In plasma, pre-b1 and -2 were rapidly (,5 min) remodeled into larger HDLs, whereas pre-b3 and -4 were remodeled into smaller HDLs. Pre-b HDLs were similarly remodeled in vitro with control or LCAT-immunodepleted plasma, but not when incubated with phospholipid transfer protein knockout plasma. Our results suggest that initial interaction of apoA-I with ABCA1 imparts a unique conformation that partially determines the in vivo metabolic fate of apoA-I, resulting in increased liver and decreased kidney catabolism as pre-b HDL particle size increases.—Mulya, A., J-Y. Lee, A. K. Gebre, E. Y. Boudyguina, S-K. Chung, T. L. Smith, P. L. Colvin, X-C. Jiang, and J. S. Parks. Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL. J. Lipid Res. 2008. 49: 2390–2401.