| A role of the bile salt receptor FXR in atherosclerosis. | |
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MedLine Citation:
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PMID: 20631352 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly via the bile salt receptors FXR and TGR5. Activation of FXR has been shown to improve plasma lipid profiles, whereas Fxr(-/-) mice have increased plasma triglyceride and very-low-density lipoprotein levels. Nevertheless, high-density lipoprotein cholesterol levels are increased in these mice, suggesting that FXR has both anti- and proatherosclerotic properties. Interestingly, there is increasing evidence for a role of FXR in "nonclassical" bile salt target tissues, eg, vasculature and macrophages. In these tissues, FXR has been shown to influence vascular tension and regulate the unloading of cholesterol from foam cells, respectively. Recent publications have provided insight into the antiinflammatory properties of FXR in atherosclerosis. Bile salt signaling via TGR5 might regulate energy homeostasis, which could serve as an attractive target to increase energy expenditure and weight loss. Interventions aiming to increase cholesterol turnover (eg, by bile salt sequestration) significantly improve plasma lipid profiles and diminish atherosclerosis in animal models. Bile salt metabolism and bile salt signaling pathways represent attractive therapeutic targets for the treatment of atherosclerosis. |
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Authors:
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Jurre Hageman; Hilde Herrema; Albert K Groen; Folkert Kuipers |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-15 Completed Date: 2010-08-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1519-28 Citation Subset: IM |
Affiliation:
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Laboratory of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, Hanzeplein 1, 9713 EZ Groningen, The Netherlands. j.hageman@med.umcg.nl |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / drug therapy, immunology, metabolism* Bile Acids and Salts / metabolism* Endothelial Cells / metabolism Energy Metabolism Humans Inflammation / metabolism Inflammation Mediators / metabolism Lipids / blood Macrophages / metabolism Muscle, Smooth, Vascular / metabolism Obesity / metabolism Receptors, Cytoplasmic and Nuclear / metabolism* Receptors, G-Protein-Coupled / metabolism* Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/GPBAR1 protein, human; 0/Inflammation Mediators; 0/Lipids; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, G-Protein-Coupled; 0/farnesoid X-activated receptor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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