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Toxicity with LXR agonists – Problem solving activities for mechanistic understanding
AstraZeneca R&D, Mölndal, Sweden.
AstraZeneca R&D, Södertälje, Sweden.
AstraZeneca R&D, Södertälje, Sweden.
Global Safety Assessment AstraZeneca, Macclesfield, United Kingdom.
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2012 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Suppl. (S), S39-S39 p.Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Several lines of evidence points toward the potential positive effects of LXR (Liver X Receptor) modulators for effective and safe therapy of cardiovascular diseases (CVDs). LXR is a dimeric nuclear hormone receptor that exists as a combination of RXR and one of two subtypes LXR alpha or beta, which act as cholesterol sensors. LXR alpha is highly expressed in the liver, intestine and adipose tissue while LXR beta is ubiquitously expressed. Activation of LXR up-regulates several genes involved in reverse cholesterol transport (RCT), including ABC transporters. This results in increased efflux of cholesterol from macrophages in atherosclerotic vascular lesions to the circulation and further on to other tissues to ultimately be excreted into the faeces. These effects together with systemic and local anti-inflammatory properties of LXR modulation are likely to contribute to decreased atherosclerosis. The positive effects of LXR activation on RCT and cholesterol balance must be obtained without negative lipid effects, since LXR also activates lipogenic genes. Other types of toxicity and approaches to better understand the mechanism(s) behind these will be presented. Copyright © 2012 Published by Elsevier Ireland Ltd.

Place, publisher, year, edition, pages
Shannon: Elsevier, 2012. Vol. 211, no Suppl. (S), S39-S39 p.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:hh:diva-28241DOI: 10.1016/j.toxlet.2012.03.163ISI: 000305173900125OAI: oai:DiVA.org:hh-28241DiVA: diva2:811230
Conference
EUROTOX 2012, 48th Congress of the European Societies of Toxicology, Stockholm, Sweden, 17-20 June, 2012
Available from: 2015-05-11 Created: 2015-05-11 Last updated: 2015-05-11Bibliographically approved

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Lutz, Mareike
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CiteExportLink to record
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Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
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  • de-DE
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  • nn-NO
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