Nicorandil Inhibits Cyclic Strain-Induced Interleukin-8 Expression in Human Umbilical Vein Endothelial Cells

Hung Hsing Chao, Hong Jye Hong, Tzu Hurng Cheng, Neng Lang Shih, Shih Hurng Loh, Ju Chi Liu, Jin Jer Chen, Li-Chin Sung

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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. Summary: 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. Key Messages: 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.

Original languageEnglish
Pages (from-to)42-50
Number of pages9
JournalPharmacology
DOIs
Publication statusAccepted/In press - Apr 7 2016

Keywords

  • Endothelial cells
  • Heme oxygenase-1
  • Interleukin-8#
  • Nicorandil

ASJC Scopus subject areas

  • Pharmacology

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