Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages

Elda Favari, Francesca Zimetti, Anna E. Bortnick, Maria Pia Adorni, Ilaria Zanotti, Monica Canavesi, Franco Bernini

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.

Original languageEnglish (US)
Pages (from-to)6537-6542
Number of pages6
JournalFEBS Letters
Volume579
Issue number29
DOIs
StatePublished - Dec 5 2005
Externally publishedYes

Keywords

  • ATP-binding cassette A1
  • Atherosclerosis
  • Cholesterol efflux
  • Foam cells
  • Macrophages
  • Oxidized low density lipoprotein

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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