| First Author | Guo GL | Year | 2006 |
| Journal | Biochim Biophys Acta | Volume | 1761 |
| Issue | 12 | Pages | 1401-9 |
| PubMed ID | 17110163 | Mgi Jnum | J:118172 |
| Mgi Id | MGI:3698703 | Doi | 10.1016/j.bbalip.2006.09.018 |
| Citation | Guo GL, et al. (2006) Effects of FXR in foam-cell formation and atherosclerosis development. Biochim Biophys Acta 1761(12):1401-9 |
| abstractText | Farnesoid X receptor (FXR), a bile-acid-activated member of the 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. The 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 in 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 disruption of the FXR gene could attenuate 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. |
