title: Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein.
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.
authors: Department of Chemistry Northwestern University, Evanston, IL 60208.
authors: Andrea J
authors: AJ
authors: Luthi
authors: Lipid Research Group, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
authors: Nicholas N
authors: NN
authors: Lyssenko
authors: Lipid Research Group, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
authors: Duyen
authors: D
authors: Quach
authors: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611 Walter S. and Lucienne Driskill Graduate Training Program in Life Sciences, Northwestern University, Chicago, IL 60611 Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors: Kaylin M
authors: KM
authors: McMahon
authors: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
authors: John S
authors: JS
authors: Millar
authors: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors: Kasey C
authors: KC
authors: Vickers
authors: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
authors: Daniel J
authors: DJ
authors: Rader
authors: Lipid Research Group, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
authors: Michael C
authors: MC
authors: Phillips
authors: Department of Chemistry Northwestern University, Evanston, IL 60208 International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
authors: Chad A
authors: CA
authors: Mirkin
authors: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208 Simpson Querrey Institute for BioNanotechnology and Medicine, Northwestern University, Chicago, IL 60611.
authors: C Shad
authors: CS
authors: Thaxton
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000188:drug therapy; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D006046:Gold / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D018716:Molecular Mimicry; D053758:Nanoparticles / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology; D051122:Scavenger Receptors, Class B / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D002316:Cardiotonic Agents; D002784:Cholesterol; D006046:Gold; D008074:Lipoproteins; D010743:Phospholipids; D051122:Scavenger Receptors, Class B; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C454739:Scarb1 protein, mouse
keywords: ATP-binding cassette transporter A1; ATP-binding cassette transporter G1; atherosclerosis; cholesterol efflux; macrophages; scavenger receptor class B type I
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