Abstract
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 < 0.01) and 60% (P < 0.001), respectively. Interestingly, deficiency of PXR reduced the expression levels of CD36, lipid accumulation, and CD36-mediated oxidized LDL uptake in peritoneal macrophages of PXR(-/-)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.
Highlights
The pregnane X receptor (PXR, known as steroid and xenobiotic receptor (SXR)) is a nuclear hormone receptor activated by xenobiotics as well as diverse sterols and their metabolites
We investigate the pathological effects of PXR deficiency on the development of atherosclerosis in apoEϪ/Ϫ mice
PXRϪ/ϪapoEϪ/Ϫ mice have similar plasma lipid levels and cholesterol distribution patterns compared with apoEϪ/Ϫ mice but significantly decreased atherosclerotic lesion areas in both the aortic root
Summary
The pregnane X receptor (PXR, known as SXR) is a nuclear hormone receptor activated by xenobiotics as well as diverse sterols and their metabolites. Recent evidence indicates that PXR may 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. We show that deficiency of PXR did not alter plasma triglyceride and cholesterol levels in apoE؊/؊ mice. Deficiency of PXR reduced the expression levels of CD36, lipid accumulation, and CD36-mediated oxidized LDL uptake in peritoneal macrophages of PXR؊/؊apoE؊/؊ mice. 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.— Sui, Y., J.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
