出版社：American Society for Biochemistry and Molecular Biology
摘要：The pregnane X receptor (PXR, also known as SXR) is a nuclear hormone receptor activated by xenobiotics as well as diverse sterols and their metabolites. PXR functions as a xenobiotic sensor to coordinately regulate xenobiotic metabolism via transcriptional regulation of xenobiotic-detoxifying enzymes and transporters. Recent evidence indicates that PXR may also play an important role in lipid homeostasis and atherosclerosis. To define the role of PXR in atherosclerosis, we generated PXR and apoE double knockout (PXR−/−apoE−/−) mice. Here we show that deficiency of PXR did not alter plasma triglyceride and cholesterol levels in apoE−/− mice. However, PXR−/−apoE−/− mice had significantly decreased atherosclerotic cross-sectional lesion area in both the aortic root and brachiocephalic artery by 40% ( P P −/−apoE−/− mice. Furthermore, immunofluorescence staining showed that PXR and CD36 were expressed in the atherosclerotic lesions of apoE−/− mice, and the expression levels of PXR and CD36 were diminished in the lesions of PXR−/−apoE−/− mice. Our findings indicate that deficiency of PXR attenuates atherosclerosis development, which may result from decreased CD36 expression and reduced lipid uptake in macrophages.
关键词：pregnane X receptor ; macrophage ; foam cell ; apolipoprotein E ; lipid homeostasis
