The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake

Nancy R. Webb, Lei Cai, Kristine S. Ziemba, Jin Yu, Mark S. Kindy, Deneys R. Van Der Westhuyzen, Frederick C. De Beer

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Scavenger receptor class B type I (SR-BI) delivers cholesterol ester from HDL to cells via a selective uptake mechanism, whereby lipid is transferred from the core of the particle without concomitant degradation of the protein moiety. The precise metabolic fate of HDL particles after selective lipid uptake is not known. To characterize SR-BI-mediated HDL processing in vivo, we expressed high levels of this receptor in livers of apoA-I-/- mice by adenoviral vector gene transfer, and then injected the mice with a bolus of human HDL2 traced with 125I-dilactitol tyramine. HDL recovered from apoA-I-/- mice over-expressing SR-BI was significantly smaller than HDL recovered from control mice as measured by non-denaturing gel electrophoresis. When injected into C57BL/6 mice, these HDL "remnants" were rapidly converted to HDL2-sized lipoprotein particles, and were cleared from the plasma at a rate similar to HDL2. In assays in cultured cells, HDL remnants did not stimulate ATP-binding cassette transporter A1-dependent cholesterol efflux. When mixed with mouse plasma ex vivo, HDL remnants rapidly converted to larger HDL particles. These studies identify a previously ill-defined pathway in HDL metabolism, whereby SR-BI generates small, dense HDL particles that are rapidly remodeled in plasma. This remodeling pathway may represent a process that is important in determining the rate of apoA-I catabolism and HDL-mediated reverse cholesterol transport.

Original languageEnglish
Pages (from-to)1890-1898
Number of pages9
JournalJournal of Lipid Research
Volume43
Issue number11
DOIs
StatePublished - Nov 1 2002

Keywords

  • ABCA1
  • Adenovirus
  • Lipoprotein
  • Mouse
  • Reverse cholesterol transport
  • Scavenger receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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