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Record number 407379
Title A Role of the Bile Salt Receptor FXR in Atherosclerosis
Author(s) Hageman, J.; Herrema, H.J.; Groen, A.K.; Kuipers, F.
Source Arteriosclerosis Thrombosis and Vascular Biology 30 (2010)8. - ISSN 1079-5642 - p. 1519 - 1528.
Department(s) Chair Nutrition Metabolism and Genomics
Publication type Refereed Article in a scientific journal
Publication year 2010
Keyword(s) farnesoid-x-receptor - low-density-lipoprotein - vascular smooth-muscle - reverse cholesterol transport - small heterodimer partner - apolipoprotein-a-i - nuclear receptor - deficient mice - acid synthesis - targeted disruption
Abstract 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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