Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL
Atherogenesis is the narrowing of arteries due to plaque build-up that results in cardiovascular disease that can lead to death. The macrophage lectin-like oxidized LDL receptor-1 (LOX-1), also called the oxidized low-density lipoprotein receptor 1 (OLR1), is currently thought to aid in atherosclero...
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doaj-9af3726bc50546e294721780f807b3e32020-11-24T22:39:18ZengHindawi LimitedJournal of Lipids2090-30302090-30492017-01-01201710.1155/2017/84794828479482Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDLDanielle W. Kimmel0William P. Dole1David E. Cliffel2Department of Chemistry, Vanderbilt University, VU Station B, Nashville, TN 37235-1822, USANovartis Institutes for Biomedical Research, 220 Massachusetts Ave. 360C, Cambridge, MA 02139, USADepartment of Chemistry, Vanderbilt University, VU Station B, Nashville, TN 37235-1822, USAAtherogenesis is the narrowing of arteries due to plaque build-up that results in cardiovascular disease that can lead to death. The macrophage lectin-like oxidized LDL receptor-1 (LOX-1), also called the oxidized low-density lipoprotein receptor 1 (OLR1), is currently thought to aid in atherosclerotic disease progression; therefore metabolic studies have potential to both provide mechanistic validation for the role of LOX-1 in disease progression and provide valuable information regarding biomarker strategies and clinical imaging. One such mechanistic study is the upregulation of LOX-1 by methylated bacterial DNA and deoxy-cytidylate-phosphate-deoxy-guanylate-DNA (CpG)-DNA exposure. CpG-DNA is known to promote oxidative burst responses in macrophages, due to its direct binding to toll-like receptor 9 (TLR9) leading to the initiation of an NF-κB mediated immune response. In addition to the upregulation of macrophage LOX-1 expression, these studies have also examined the macrophage metabolic response to murine LOX-1/OLR1 antibody exposure. Our data suggests the antibody exposure effectively blocks LOX-1 dependent oxLDL metabolic activation of the macrophage, which was quantified using the multianalyte microphysiometer (MAMP). Using the MAMP to examine metabolic fluctuations during various types of oxLDL exposure, LOX-1 upregulation and inhibition provide valuable information regarding the role of LOX-1 in macrophage activation of oxidative burst.http://dx.doi.org/10.1155/2017/8479482 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Danielle W. Kimmel William P. Dole David E. Cliffel |
spellingShingle |
Danielle W. Kimmel William P. Dole David E. Cliffel Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL Journal of Lipids |
author_facet |
Danielle W. Kimmel William P. Dole David E. Cliffel |
author_sort |
Danielle W. Kimmel |
title |
Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL |
title_short |
Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL |
title_full |
Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL |
title_fullStr |
Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL |
title_full_unstemmed |
Elucidation of the Role of Lectin-Like oxLDL Receptor-1 in the Metabolic Responses of Macrophages to Human oxLDL |
title_sort |
elucidation of the role of lectin-like oxldl receptor-1 in the metabolic responses of macrophages to human oxldl |
publisher |
Hindawi Limited |
series |
Journal of Lipids |
issn |
2090-3030 2090-3049 |
publishDate |
2017-01-01 |
description |
Atherogenesis is the narrowing of arteries due to plaque build-up that results in cardiovascular disease that can lead to death. The macrophage lectin-like oxidized LDL receptor-1 (LOX-1), also called the oxidized low-density lipoprotein receptor 1 (OLR1), is currently thought to aid in atherosclerotic disease progression; therefore metabolic studies have potential to both provide mechanistic validation for the role of LOX-1 in disease progression and provide valuable information regarding biomarker strategies and clinical imaging. One such mechanistic study is the upregulation of LOX-1 by methylated bacterial DNA and deoxy-cytidylate-phosphate-deoxy-guanylate-DNA (CpG)-DNA exposure. CpG-DNA is known to promote oxidative burst responses in macrophages, due to its direct binding to toll-like receptor 9 (TLR9) leading to the initiation of an NF-κB mediated immune response. In addition to the upregulation of macrophage LOX-1 expression, these studies have also examined the macrophage metabolic response to murine LOX-1/OLR1 antibody exposure. Our data suggests the antibody exposure effectively blocks LOX-1 dependent oxLDL metabolic activation of the macrophage, which was quantified using the multianalyte microphysiometer (MAMP). Using the MAMP to examine metabolic fluctuations during various types of oxLDL exposure, LOX-1 upregulation and inhibition provide valuable information regarding the role of LOX-1 in macrophage activation of oxidative burst. |
url |
http://dx.doi.org/10.1155/2017/8479482 |
work_keys_str_mv |
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