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Circadian rhythms govern cardiac repolarization and arrhythmogenesis

唐唐添加于 2012-2-29 20:45 | 1691 次阅读 | 0 个评论

作者
Jeyaraj D, Haldar SM, Wan X, McCauley MD, Ripperger JA, Hu K, Lu Y, Eapen BL, Sharma N, Ficker E, Cutler MJ, Gulick J, Sanbe A, Robbins J, Demolombe S, Kondratov RV, Shea SA, Albrecht U, Wehrens XHT, Rosenbaum DS, Jain MK
摘要
Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease1, 2, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure)3, 4, 5 or pattern (for example, Brugada’s syndrome)6 of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, krüppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current7. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.
详细资料
- 文献种类: Journal Article
- 期刊名称: Nature
- 期刊缩写: Nature
- 期卷页: 2012年第483卷第7387期 96-99页
- ISBN: 0028-0836
学科领域工程技术 » 管理学
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