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Cited by 91Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipid metabolism and disorders

Non-redundant roles for LXR and LXR in atherosclerosis susceptibility in low density lipoprotein receptor knockout mice

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Bischoff, E. D., Daige, C. L., Petrowski, M., Dedman, H., Pattison, J., Juliano, J., Li, A. C., Schulman, I. G.·2010·The Journal of Lipid Research
DOI 10.1194/jlr.m900096PMC PMC2853457
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Abstract

The liver X receptors LXRalpha and LXRbeta play critical roles in maintaining lipid homeostasis by functioning as transcription factors that regulate genetic networks controlling the transport, catabolism, and excretion of cholesterol. The studies described in this report examine the individual anti-atherogenic activity of LXRalpha and LXRbeta and determine the ability of each subtype to mediate the biological response to LXR agonists. Utilizing individual knockouts of LXRalpha and LXRbeta in the Ldlr(-/-) background, we demonstrate that LXRalpha has a dominant role in limiting atherosclerosis in vivo. Functional studies in macrophages indicate that LXRalpha is required for a robust response to LXR ligands, whereas LXRbeta functions more strongly as a repressor. Furthermore, selective knockout of LXRalpha in hematopoietic cells and rescue experiments indicate that the anti-atherogenic activity of this LXR subtype is not restricted to macrophages. These studies indicate that LXRalpha plays a selective role in limiting atherosclerosis in response to hyperlipidemia.

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Authors
Bischoff, E. D., Daige, C. L., Petrowski, M., Dedman, H., Pattison, J., Juliano, J., Li, A. C., & Schulman, I. G.
Affiliations
  • Exelixis (United States) (US)
  • University of California San Diego (US)
  • University of Virginia Health System (US)
ORCID
Venue
The Journal of Lipid Research
Publisher
Elsevier BV
Published
2010-04-13
Volume
51
Issue
5
Pages
900-906
ISSN
0022-2275 (ISSN-L)
DOI
10.1194/jlr.m900096
PMC
PMC2853457
OpenAlex
W2150034417
Cited by
91
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 11 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 15 · 2012: 7
FWCI
11.15
Type
journal article
Language
en
Open access
Locations
  • Journal of Lipid Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Virginia
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL087391, R01HL087391)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
liver X receptor alpha, liver X receptor beta, atherosclerosis, LXR agonists, macrophages, hematopoietic cells, hyperlipidemia, cholesterol homeostasis, transcriptional repression, anti-atherogenic activity
MeSH terms
Liver X Receptors, Animals, Bone Marrow Cells, Disease Susceptibility, Gene Expression Regulation, Macrophages, Male, Receptors, LDL, Mice, Knockout, Atherosclerosis, Mice, Gene Knockout Techniques, Orphan Nuclear Receptors

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