title: Nicorandil Inhibits Cyclic Strain-Induced Interleukin-8 Expression in Human Umbilical Vein Endothelial Cells.
abstract: BACKGROUND
  Nicorandil, a mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channel opener, exerts protective effects on the cardiovascular system. This study examined the effect of nicorandil on cyclic strain-induced interleukin-8 (IL-8) expression in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  Cultured HUVECs were exposed to cyclic strain in the presence or absence of nicorandil (1-10 μmol/l); we then analyzed IL-8 expression. We also assessed the effects of nicorandil on heme oxygenase-1 (HO-1) expression and cyclic strain-modulated IL-8 expression after HO-1 silencing in HUVECs.
  
  
  CONCLUSIONS
  HUVECs exposed to cyclic strain showed increased IL-8 messenger RNA expression and protein secretion. Nicorandil (1-10 μmol/l) inhibited cyclic strain-induced IL-8 expression, whereas 5-hydroxydecanoate (100 μmol/l), a selective inhibitor of the mitoKATP channel, completely reversed the inhibitory effects of nicorandil on cyclic strain-induced IL-8 expression. We demonstrated that nicorandil increased HO-1 expression in HUVECs. In addition, cobalt protoporphyrin (10 μmol/l), an inducer of HO-1 expression, mimicked the effects of nicorandil and inhibited IL-8 expression under cyclic strain, whereas zinc protoporphyrin IX (10 μmol/l), an inhibitor of HO-1 expression, antagonized the effect of nicorandil. HO-1 silencing significantly abrogated the inhibitory effects of nicorandil on cyclic strain-induced IL-8 expression, suggesting that HO-1 plays a role in the mechanism of action of nicorandil.
  
  
  CONCLUSIONS
  This study is the first to report that nicorandil inhibits cyclic strain-induced IL-8 expression through the induction of HO-1 expression in HUVECs. This finding provides valuable new insight into the molecular pathways contributing to the vasoprotective effects of nicorandil.
authors.affiliation: Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Hung-Hsing
authors.initials: HH
authors.lastname: Chao
authors.forename: Hong-Jye
authors.initials: HJ
authors.lastname: Hong
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.forename: Neng-Lang
authors.initials: NL
authors.lastname: Shih
authors.forename: Shih-Hurng
authors.initials: SH
authors.lastname: Loh
authors.forename: Ju-Chi
authors.initials: JC
authors.lastname: Liu
authors.forename: Jin-Jer
authors.initials: JJ
authors.lastname: Chen
authors.forename: Li-Chin
authors.initials: LC
authors.lastname: Sung
mesh_terms: D001696:Biomechanical Phenomena; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013314:Stress, Mechanical
chemical_list: C508606:CXCL8 protein, human; D002317:Cardiovascular Agents; D016209:Interleukin-8; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020108:Nicorandil; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1