出版社：American Society for Biochemistry and Molecular Biology
摘要：The liver X receptors LXRα and LXRβ play critical roles in maintaining lipid homeostasis by functioning as transcription factors that regulate genetic networks controlling the transport, catabolism, and excretion of cholesterol. The studies described in this report examine the individual anti-atherogenic activity of LXRα and LXRβ and determine the ability of each subtype to mediate the biological response to LXR agonists. Utilizing individual knockouts of LXRα and LXRβ in the Ldlr −/− background, we demonstrate that LXRα has a dominant role in limiting atherosclerosis in vivo. Functional studies in macrophages indicate that LXRα is required for a robust response to LXR ligands, whereas LXRβ functions more strongly as a repressor. Furthermore, selective knockout of LXRα in hematopoietic cells and rescue experiments indicate that the anti-atherogenic activity of this LXR subtype is not restricted to macrophages. These studies indicate that LXRα plays a selective role in limiting atherosclerosis in response to hyperlipidemia.
