Effects of FXR in foam-cell formation and atherosclerosis development
| Autor: | Taro E. Akiyama, Beverly Paigen, Grace L. Guo, Silvia Santamarina-Fojo, Marcelo Amar, Frank J. Gonzalez, Bryan H. Brewer |
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| Rok vydání: | 2006 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty CD36 Biological Transport Active Gene Expression Receptors Cytoplasmic and Nuclear In Vitro Techniques Article Mice chemistry.chemical_compound Apolipoproteins E Internal medicine Hyperlipidemia medicine Animals Homeostasis Molecular Biology Foam cell Mice Knockout biology Cholesterol Cholesterol LDL Cell Biology Triglyceride homeostasis Atherosclerosis medicine.disease Lipids DNA-Binding Proteins Lipoproteins LDL Mice Inbred C57BL Endocrinology Nuclear receptor chemistry Macrophages Peritoneal biology.protein Cytokines Female lipids (amino acids peptides and proteins) Farnesoid X receptor Foam Cells Transcription Factors |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1761:1401-1409 |
| ISSN: | 1388-1981 |
| DOI: | 10.1016/j.bbalip.2006.09.018 |
| Popis: | Farnesoid X receptor (FXR), a bile-acid-activated transcriptional factor and a member of the hormone nuclear receptor superfamily, is essential in regulating bile-acid, cholesterol, and triglyceride homeostasis. Disruption of the FXR gene in mice results in a proatherosclerotic lipid profile with increased serum cholesterols and triglycerides. However, the role of FXR in foam-cell formation and atherosclerosis development remains unclear. Our current study showed that the peritoneal macrophages isolated from FXR-null mice took up less oxidized LDL-cholesterol (oxLDL-C), which was accompanied by a marked reduction of CD36 expression in these cells. This result appears to be FXR-independent, as FXR was not detected in the peritoneal macrophages. To assess to what extent FXR modulates atherosclerosis development, FXR/ApoE double-null mice were generated. Female mice were used for atherosclerosis analysis. Compared to ApoE-null mice, the FXR/ApoE double-null mice were found to have less atherosclerotic lesion area in the aorta, despite a further increase in the serum cholesterols and triglycerides. Our results indicate that deletion of the FXR gene could attenuate the atherosclerosis development, most likely resulting from reduced oxLDL-C uptake by macrophages. Our study cautions the use of serum lipid levels as a surrogate marker to determine the efficiency of FXR modulators in treating hyperlipidemia. |
| Databáze: | OpenAIRE |
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