Nicorandil modulated macrophages activation and polarization via NF-κb signaling pathway.
Nicorandil, a drug with both nitrate-like and ATP-sensitive potassium (KATP) channel-activating properties, has been well demonstrated in various aspects of myocardial infarction (MI), especially in inhibiting cell apoptosis and increasing coronary flow. However, the role of nicorandil in regulating inflammation and angiogenesis following myocardial infarction is still unrevealed. In the present study, we explored the effect of nicorandil on macrophage phenotype transition and inflammation regulation and the potential underlying mechanisms. For the phenotype transition and phagocytosis ability of macrophages detection, flow cytometry analysis was used. The inflammation factors were measured with ELISA and qRT-PCR. Western blot was used to assess the levels of NF-κb and its target genes and VEGF expression. The tube formation ability of endothelial cells was examined on matrigel. We discovered that nicorandil can obviously inhibit the differentiation of monocytes into mature macrophages and decrease M1 phenotype transition both in peritoneal macrophages and cultured macrophage cell line in normal or hypoxia and serum deprivation (H/SD) conditions. Meanwhile, nicorandil can induce an anti-inflammatory M2 phenotype. Thereby, nicorandil regulated macrophages switching to M1/M2 status. Our data further showed that NF-κb and the expression of its target genes were pivotal players in the regulation of macrophages phenotype. Besides, we also showed that nicorandil can promote the tube formation and VEGF expression in endothelial cells. We concluded that nicorandil may serve as an effective modulator of NF-κb signaling pathway during the pathogenesis of MI via regulating M1/M2 status and promoting angiogenesis.
['Zhang|Fengyun|F|', 'Xuan|Yongli|Y|', 'Cui|Jinjin|J|', 'Liu|Xinxin|X|', 'Shao|Zhiying|Z|', 'Yu|Bo|B|']
D000818:Animals D000959:Antihypertensive Agents D017209:Apoptosis D002454:Cell Differentiation D002460:Cell Line D002470:Cell Survival D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D007249:Inflammation D008262:Macrophage Activation D008264:Macrophages D051379:Mice D008810:Mice, Inbred C57BL D018919:Neovascularization, Physiologic D020108:Nicorandil D010587:Phagocytosis D015221:Potassium Channels D017382:Reactive Oxygen Species D051996:Transcription Factor RelA D042461:Vascular Endothelial Growth Factor A
Nicorandil Macrophages Inflammation Angiogenesis B signaling pathway NF-&kappa