Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein

Andrea J. Luthi, Nicholas N. Lyssenko*, Duyen Quach, Kaylin M. McMahon, John S. Millar, Kasey C. Vickers, Daniel J. Rader, Michael C. Phillips, Chad A. Mirkin, C. Shad Thaxton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The ability of HDL to support macrophage cholesterol efflux is an integral part of its atheroprotective action. Augmenting this ability, especially when HDL cholesterol efflux capacity from macrophages is poor, represents a promising therapeutic strategy. One approach to enhancing macrophage cholesterol efflux is infusing blood with HDL mimics. Previously, we reported the synthesis of a functional mimic of HDL (fmHDL) that consists of a gold nanoparticle template, a phospholipid bilayer, and apo A-I. In this work, we characterize the ability of fmHDL to support the well-established pathways of cellular cholesterol efflux from model cell lines and primary macrophages. fmHDL received cell cholesterol by unmediated (aqueous) and ABCG1- and scavenger receptor class B type I (SR-BI)-mediated diffusion. Furthermore, the fmHDL holoparticle accepted cholesterol and phospholipid by the ABCA1 pathway. These results demonstrate that fmHDL supports all the cholesterol efflux pathways available to native HDL and thus, represents a promising infusible therapeutic for enhancing macrophage cholesterol efflux. fmHDL accepts cholesterol from cells by all known pathways of cholesterol efflux: unmediated, ABCG1- and SR-BI-mediated diffusion, and through ABCA1.

Original languageEnglish (US)
Pages (from-to)972-985
Number of pages14
JournalJournal of lipid research
Volume56
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • ATP-binding cassette transporter G1
  • Atherosclerosis
  • Cholesterol efflux
  • Macrophages
  • Scavenger receptor class B type I
  • Supplementary ATP-binding cassette transporter A1

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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