title: Chemerin/ChemR23 signaling axis is involved in the endothelial protection by K(ATP) channel opener iptakalim.
abstract: OBJECTIVE
  To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of K(ATP) channels and to determine the role of the chemerin/ChemR23 axis in the iptakalim-mediated endothelial protection.
  
  
  METHODS
  Cultured rat aortic endothelial cells (RAECs) were used. Chemerin secretion and ChemR23 protein expression were investigated using Western blot analysis. The gene expression level of ChemR23 was examined with RT-PCR. In addition, the release of nitric oxide (NO) was measured with a nitric oxide assay.
  
  
  RESULTS
  Homocysteine, uric acid, high glucose, or oxidized low-density lipoprotein (ox-LDL) down-regulated the chemerin secretion and ChemR23 gene/protein expression in RAECs as a function of concentration and time, which was reversed by pretreatment with iptakalim (1-10 μmol/L). Moreover, these effects of iptakalim were abolished in the presence of the K(ATP) channel antagonist glibenclamide (1 μmol/L). Both iptakalim and recombinant chemerin restored the impaired NO production in RAECs induced by uric acid, and the effects were abolished by anti-ChemR23 antibodies.
  
  
  CONCLUSIONS
  Iptakalim via opening K(ATP) channels enhanced the endothelial chemerin/ChemR23 axis and NO production, thus improving endothelial function.
authors.affiliation: Department of Environmental Medicine, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Rui-jun
authors.initials: RJ
authors.lastname: Zhao
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D018925:Chemokines; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011437:Propylamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D054392:Adipokines; D018925:Chemokines; C109811:Cmklr1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; C560738:Rarres2 protein, rat; D019707:Receptors, Chemokine; D009569:Nitric Oxide