Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL |
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Authors: | Mulya Anny Lee Ji-Young Gebre Abraham K Boudyguina Elena Y Chung Soon-Kyu Smith Thomas L Colvin Perry L Jiang Xian-Cheng Parks John S |
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Institution: | Department of Pathology, Wake Forest University Health Sciences, Winston-Salem, NC, USA. |
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Abstract: | We investigated the in vivo metabolic fate of pre-beta HDL particles in human apolipoprotein A-I transgenic (hA-I (Tg)) mice. Pre-beta HDL tracers were assembled by incubation of (125)I]tyramine cellobiose-labeled apolipoprotein A-I (apoA-I) with HEK293 cells expressing ABCA1. Radiolabeled pre-beta HDLs of increasing size (pre-beta1, -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-beta2, -3, and -4 had similar plasma die-away rates, whereas pre-beta1 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-beta HDL size increased. In plasma, pre-beta1 and -2 were rapidly (<5 min) remodeled into larger HDLs, whereas pre-beta3 and -4 were remodeled into smaller HDLs. Pre-beta 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-beta HDL particle size increases. |
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Keywords: | Apolipoprotein A-I phospholipid transfer protein lecithin:cholesterol acyltransferase in vivo catabolism high density lipoproteins ABCA1 transporter |
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