Sudden cardiac death (SCD) secondary to ventricular arrhythmia is the most common cause of mortality from cardiovascular disease worldwide. Despite decades of investigation, a thorough understanding of triggers and effective pharmacologic treatments for SCD are lacking and the primary treatment remains mechanical defibrillation. This sobering reality has led to the view that a complete re-examination of the fundamental mechanisms underlying the development of SCD is needed to provide a foundation for the development of novel, effective therapies.           Biological processes that oscillate with a 24-hour periodicity are termed circadian. All cells have a circadian clock that synchronizes changes in gene expression with rhythmic patterns of daily life, i.e. eating or sleeping. The observation that SCD exhibits a peak during early morning, is increased in shift workers suggests that circadian influences may be operative. However, a direct link between the circadian clock, metabolism, and cardiac electrical activity was lacking. In this regard, recent studies from our laboratory identified the first molecular link between endogenous circadian rhythms and SCD. Specifically, we reported that a specific cardiac ion channel that controls myocyte repolarization exhibited circadian oscillation under the control of the clock-dependent oscillator KLF15. Alterations in KLF15 levels in vivo rendered animals susceptible to SCD. Finally, the observation that KLF15 is altered in subjects with heart failure and Brugada syndrome suggests that the study of this pathway may have implications for human disease.

KLF15 links the circadian clock to arrhythmogenesis

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.