Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein
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 cholest...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520312372 |
| _version_ | 1818658499132915712 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Andrea J. Luthi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T03:58:20Z |
| format | Article |
| id | doaj.art-cbf0a92bb5874c11a69dc96e5efce1af |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T03:58:20Z |
| publishDate | 2015-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-cbf0a92bb5874c11a69dc96e5efce1af2022-12-21T22:04:34ZengElsevierJournal of Lipid Research0022-22752015-05-01565972985Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoproteinAndrea J. Luthi0Nicholas N. Lyssenko1Duyen Quach2Kaylin M. McMahon3John S. Millar4Kasey C. Vickers5Daniel J. Rader6Michael C. Phillips7Chad A. Mirkin8C.Shad Thaxton9Department of Chemistry Northwestern University, Evanston, IL 60208To whom correspondence should be addressed.; To whom correspondence should be addressed.; 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; To whom correspondence should be addressed.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 19104Robert 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 60611Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104Lipid 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 19104Department of Chemistry Northwestern University, Evanston, IL 60208; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208To whom correspondence should be addressed.; 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; To whom correspondence should be addressed.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.http://www.sciencedirect.com/science/article/pii/S0022227520312372ATP-binding cassette transporter A1atherosclerosismacrophagescholesterol effluxATP-binding cassette transporter G1scavenger receptor class B type I |
| spellingShingle | 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 Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein Journal of Lipid Research ATP-binding cassette transporter A1 atherosclerosis macrophages cholesterol efflux ATP-binding cassette transporter G1 scavenger receptor class B type I |
| title | Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein |
| title_full | Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein |
| title_fullStr | Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein |
| title_full_unstemmed | Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein |
| title_short | Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein |
| title_sort | robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein |
| topic | ATP-binding cassette transporter A1 atherosclerosis macrophages cholesterol efflux ATP-binding cassette transporter G1 scavenger receptor class B type I |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520312372 |
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