Nicorandil inhibits serum starvation-induced apoptosis in vascular endothelial cells.
The Impact Of Nicorandil in Angina (IONA) randomized trial showed a significant reduction in coronary events, in patients with stable angina treated with a KATP channel opener, nicorandil. However, the impact of nicorandil on endothelial apoptosis remains to be examined. We tested the hypothesis that nicorandil has anti-apoptotic effects in endothelial cells (ECs). Apoptosis was induced by serum starvation in the culture media in human umbilical vein endothelial cells. We examined the effects of nicorandil on endothelial cell apoptosis. Cell viability after serum starvation was significantly higher in the nicorandil-treated group compared with the control group (81 +/- 8% vs. 63 +/- 3%, P < 0.01). Apoptosis, as detected by caspase 3 activation and Hoechst 33258 assay, induced by serum starvation was also effectively abrogated by the treatment of nicorandil (100 muM). The protective effects of nicorandil on endothelial survival were significantly inhibited by a specific mitochondrial KATP channel blocker, 5-Hydroxydecanoic acid. A mitochondrial permeability transition pore activator significantly abolished the anti-apoptotic effect of nicorandil in endothelial cells, indicating that the mechanism of protective effect of nicorandil is involved in the mitochondrial apoptotic pathway although it affects neither Bcl-2 nor Bax protein expression levels. In conclusion, nicorandil inhibits serum starvation-induced endothelial cell apoptosis possibly through mitochondrial KATP channels.
Date
Taro
T
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Nishi-shinbashi, Tokyo, Japan. datet@jikei.ac.jp
Taniguchi
Ikuo
I
Inada
Keiichi
K
Matsuo
Seiichiro
S
Miyanaga
Satoru
S
Yamane
Teiichi
T
Abe
Yuuichi
Y
Sugimoto
Ken-Ichi
K
Mochizuki
Seibu
S
D000787:Angina Pectoris / Q000188:drug therapy; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003652:Decanoic Acids / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D020108:Nicorandil / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis
D001562:Benzimidazoles; D016895:Culture Media, Serum-Free; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019253:Proto-Oncogene Proteins c-bcl-2; C447680:hoechst 32258; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; C052853:5-hydroxydecanoic acid