Abstract 10626: Circadian Expression of Ion Channel Transcripts in Failing Human Hearts
Introduction: In rodent hearts, ~5-10% of genes show a circadian expression pattern. Despite a circadian pattern of arrhythmias in humans, no circadian expression analysis of Genes Relevant to Arrhythmias (GRA) has been reported.
Hypothesis: We tested the hypothesis that genes plausibly relevant to arrhythmias display a circadian pattern of expression in the human heart.
Methods: RNA was isolated from the LV (left ventricle) of 46 end-stage heart failure patients (age 46.3+/-14 years; 29M/17F) collected at the time of cardiac transplantation. All patients had non-ischemic cardiomyopathy and no history of arrhythmia, discharge of defibrillators, or a ventricular pacing frequency >1%. The sample timepoints were distributed around a 24 hour period (inter-timepoint mean 0.51+/-0.42 hrs). RT-PCR was performed for 5 genes whose transcripts (reference) show circadian expression in rodent hearts, and 22 Genes Relevant to electrophysiological functions and Arrhythmogenesis (GRA). Expression levels were calculated from a sliding mean of 11 consecutive timepoints (yielding 46 sliding mean timepoints) and analyzed with a cosine function. Acrophase (time of peak expression, military time) and percentage of rhythm (expression variation ascribed to circadian expression) were calculated.
Results: Four of five control transcripts (BMAL (Figure), per2, DBP, NR1D1) showed a significant (p<10-6) circadian expression with a percentage rhythm of 83-96%. Except for DBP, their respective acrophases (23:10, 11:00, 14:45, 06:00) closely approximated their acrophase times reported in rodent hearts. Of the 22 GRA transcripts, 14 (including 6 shown in Table; SCN5a shown in Figure) showed a significant (p<10-6) circadian expression pattern with 54-84% of the expression variance ascribed to a circadian rhythym.
Conclusion: Ion channel genes display a circadian pattern of RNA expression in failing human hearts and could contribute to a circadian pattern of arrhythmias.
- © 2013 by American Heart Association, Inc.