Background
- Ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD) show a circadian pattern of occurrence in heart failure patients. In the rodent ventricle, a significant portion of genes, including some ion channels, shows a circadian pattern of expression. However genes that define electrophysiologic properties in failing human heart ventricles have not been examined for a circadian expression pattern.
Methods
- Ventricular tissue samples were collected from patients at the time of cardiac transplantation. Two sets of samples (n=37 and 46, one set with a greater arrhythmic history) were selected to generate pseudo-time series according to their collection time. A third set (n=27) of samples was acquired from the non-failing ventricles of brain-dead donors. The expression of 5 known circadian clock genes and 19 additional ion channel genes plausibly important to electrophysiologic properties were analyzed by RT-PCR, and then analyzed for the percentage of expression variation attributed to a 24 hour circadian pattern.
Results
- The 5 known circadian clock gene transcripts showed a strong circadian expression pattern. Compared to rodent hearts, the human circadian clock gene transcripts showed a similar temporal order of acrophases but with a ~ 7.6 hours phase shift. Five of the ion channel genes also showed strong circadian expression. Comparable studies of circadian clock gene expression in samples recovered from non-heart failure brain-dead donors showed acrophase shifts, or weak or complete loss of circadian rhythmicity, suggesting alterations in circadian gene expression.
Conclusions
- Ventricular tissue from failing human hearts display a circadian pattern of circadian clock gene expression, but phase-shifted relative to rodent hearts. At least 5 ion channels show a circadian expression pattern in the ventricles of failing human hearts, which may underlie a circadian pattern of VT/SCD. Non-failing hearts from brain-dead donors show marked differences in circadian clock gene expression patterns, suggesting fundamental deviations from circadian expression.
Circadian Pattern of Ion Channel Gene Expression in Failing Human Hearts
