Nomiyama Takashi, Bruemmer Dennis
Division of Endocrinology and Molecular Medicine, Department of Internal Medicine, University of Kentucky College of Medicine, Wethington Health Sciences Building, Room 575, 900 South Limestone Street, Lexington, KY 40536, USA.
Curr Atheroscler Rep. 2008 Feb;10(1):88-95. doi: 10.1007/s11883-008-0013-3.
The liver X receptors (LXRs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Since their initial identification more than a decade ago, LXRs have been characterized as key transcriptional regulators of lipid and carbohydrate homeostasis. LXRs are activated by the intracellular accumulation of cholesterol derivatives to stimulate cholesterol efflux and reverse cholesterol transport and excretion into the bile. Glucose functions as an LXR ligand in carbohydrate metabolism, and receptor agonism suppresses hepatic gluconeogenesis and improves insulin sensitivity. In addition to these beneficial metabolic effects, LXR ligands suppress inflammatory and proliferative responses of vascular cells and prevent the development of atherosclerosis and its complications. In this review, we summarize the important roles of LXRs in metabolism and vascular biology and discuss their implications as potential molecular drug targets for the treatment of cardiovascular diseases.
肝脏X受体（LXRs）是属于核激素受体超家族的配体激活转录因子。自十多年前首次被鉴定以来，LXRs已被表征为脂质和碳水化合物稳态的关键转录调节因子。LXRs被胆固醇衍生物的细胞内积累激活，以刺激胆固醇流出、逆转胆固醇转运并排泄到胆汁中。葡萄糖在碳水化合物代谢中作为LXR配体发挥作用，受体激动作用可抑制肝脏糖异生并改善胰岛素敏感性。除了这些有益的代谢作用外，LXR配体还可抑制血管细胞的炎症和增殖反应，并预防动脉粥样硬化及其并发症的发生。在本综述中，我们总结了LXRs在代谢和血管生物学中的重要作用，并讨论了它们作为治疗心血管疾病潜在分子药物靶点的意义。
