title: Liver X receptor agonist alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase.
abstract: OBJECTIVE
  Liver X receptors (LXRs) are key regulators of cholesterol homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms.
  
  
  METHODS
  Endothelial progenitor cells were cultured in mannitol or 30 mm glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 μm) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed.
  
  
  RESULTS
  TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs.
  
  
  CONCLUSIONS
  TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China. lixiaoxia@bjmu.edu.cn
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Song
authors.forename: Yingying
authors.initials: Y
authors.lastname: Han
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D000071518:Liver X Receptors; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D055372:AMP-Activated Protein Kinases; D005947:Glucose; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D013549:Sweetening Agents; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides