Back to Search Start Over

Toxicity with LXR agonists – Problem solving activities for mechanistic understanding

Authors :
Andersson, Patrik
Kenne, Kerstin
Glinghammar, Björn
Pointon, Amy V.
Åkerblad, Peter
Lutz, Mareike
Hovdal, Daniel
Maxvall, Ingela
Lindstedt, Eva-Lotte
Andersson, Patrik
Kenne, Kerstin
Glinghammar, Björn
Pointon, Amy V.
Åkerblad, Peter
Lutz, Mareike
Hovdal, Daniel
Maxvall, Ingela
Lindstedt, Eva-Lotte
Publication Year :
2012

Abstract

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.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1233452900
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1016.j.toxlet.2012.03.163