Journal article

+ 1 other files

Circadian rhythms govern cardiac repolarization and arrhythmogenesis

  • Jeyaraj, Darwin Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, USA - Heart and Vascular Research Center, MetroHealth campus of Case Western Reserve University, Cleveland, USA
  • Haldar, Saptarsi M. Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, USA
  • Wan, Xiaoping Heart and Vascular Research Center, MetroHealth campus of Case Western Reserve University, Cleveland, USA
  • McCauley, Mark D. Departments of Medicine and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, USA
  • Ripperger, Jürgen A. Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
  • Hu, Kun Division of Sleep Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
  • Lu, Yuan Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, USA
  • Eapen, Betty L. Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, USA
  • Sharma, Nikunj Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, USA
  • Ficker, Eckhard Heart and Vascular Research Center, MetroHealth campus of Case Western Reserve University, Cleveland, USA
  • Cutler, Michael J. Heart and Vascular Research Center, MetroHealth campus of Case Western Reserve University, Cleveland, USA
  • Gulick, James Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
  • Sanbe, Atsushi Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
  • Robbins, Jeffrey Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
  • Demolombe, Sophie Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia Antipolis, Valbonne, France
  • Kondratov, Roman V. Department of Biological, Geological and Environmental Sciences, and Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, USA
  • Shea, Steven A. Division of Sleep Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
  • Albrecht, Urs Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
  • Wehrens, Xander H. T. Departments of Medicine and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, USA
  • Rosenbaum, David S. Heart and Vascular Research Center, MetroHealth campus of Case Western Reserve University, Cleveland, USA
  • Jain, Mukesh K. Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, USA
Show more…
    22.02.2012
Published in:
  • Nature. - 2012, vol. 483, p. 96-99
English Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, 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) 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 current. 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/302192
Other files

Statistics

Document views: 8 File downloads:
  • alb_crg.pdf: 1
  • alb_crg_sm.pdf: 0