科研之友
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摘要
There is a possibility thrombus formation is closely involved in sudden cardiac death. Amiodarone, a potassium channel inhibitor, is known to reduce mortality in patients with coronary artery disease or low ejection fraction, having antithrombotic actions. Using human monocytic THP-1 cells, we investigated the effects of amiodarone on tissue factor mRNA and protein expression. The involvement of the two main potassium channels existing in THP-1 cells was also investigated. Amiodarone (10 mu M) significantly and almost completely inhibited the increase of tissue factor mRNA and protein expression induced by tumor necrosis factor-alpha (100 ng/ml). The inhibitory effects of amiodarone on tissue factor mRNA expression showed dose-dependency. Margatoxin (1 nM), a selective blocker of voltage-dependent potassium channel K(v)1.3, also inhibited tissue factor protein expression, but didn%26apos;t significantly inhibit mRNA expression. Ba2+, a blocker of inwardly rectifying potassium channel K(ir)2.1, partly inhibited the increase of tissue factor mRNA and protein expression. This is the first study that shows amiodarone inhibits tissue factor expression in monocytic cells, by inhibiting mRNA transcription. The result may correlate with the facts amiodarone has antithrombotic actions in patients under extraordinary conditions where thrombus formation is enhanced. The inhibitory effects of amiodarone on tissue factor expression are drastic, different from those of margatoxin and Ba2+. The result suggests amiodarone has an underlying mechanism to intensely inhibit tissue factor expression other than blocking K(v)1.3 and K(ir)2.1.
- 出版日期2013-2-15
