ATP binding cassette G1-dependent cholesterol efflux during inflammation

Maria C. De Beer, Ailing Ji, Anisa Jahangiri, Ashley M. Vaughan, Frederick C. De Beer, Deneys R. Van Der Westhuyzen, Nancy R. Webb

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent effl ux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A2 (sPLA2-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.

Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalJournal of Lipid Research
Volume52
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • ATP binding cassette AI
  • High density lipoprotein
  • Macrophage
  • Reverse cholesterol transport
  • Serum amyloid A

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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