Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein
| Autor: | Michael C. Phillips, Chad A. Mirkin, Daniel J. Rader, Duyen Quach, C. Shad Thaxton, Nicholas N. Lyssenko, Kasey C. Vickers, John S. Millar, Andrea J. Luthi, Kaylin M. McMahon |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
ATP-binding cassette transporter G1
Cardiotonic Agents Lipoproteins Phospholipid Drug Evaluation Preclinical QD415-436 ATP-binding cassette transporter A1 Coronary Artery Disease 030204 cardiovascular system & hematology Biology Biochemistry Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology High-density lipoprotein Drug Stability scavenger receptor class B type I Cricetinae Animals Scavenger receptor Research Articles Phospholipids 030304 developmental biology ATP Binding Cassette Transporter Subfamily G Member 1 0303 health sciences Apolipoprotein A-I Cholesterol Macrophages Molecular Mimicry Biological Transport Cell Biology Scavenger Receptors Class B ATP Binding Cassette Transporter 1 chemistry ABCG1 ABCA1 biology.protein Nanoparticles lipids (amino acids peptides and proteins) ATP-Binding Cassette Transporters Efflux Gold atherosclerosis cholesterol efflux |
| Zdroj: | Journal of Lipid Research Journal of Lipid Research, Vol 56, Iss 5, Pp 972-985 (2015) |
| ISSN: | 1539-7262 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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