Clock genes display rhythmic expression in human hearts

Area of Science:

• Cardiovascular Biology
• Chronobiology
• Molecular Cardiology

Background:

• Circadian clock genes regulate physiological processes in mammals.
• Previous studies identified clock genes in rodent hearts, linking their disruption to myocardial dysfunction.
• Limited data existed on clock gene expression and function in human hearts.

Purpose of the Study:

• To investigate the expression and circadian rhythmicity of core clock genes (PER1, PER2, BMAL1, CRY1) in human heart tissue.
• To compare clock gene expression patterns between patients with coronary heart disease, cardiomyopathy, and healthy individuals.
• To determine if human myocardial clock gene rhythms differ from those observed in rodents.

Main Methods:

• Real-time PCR was used to quantify mRNA levels of PER1, PER2, BMAL1, and CRY1.
• Circadian expression patterns were analyzed using sliding means and Cosinor functions.
• Statistical analyses (ANOVAs) compared rhythmic patterns across patient groups and healthy donors.

Main Results:

• All four clock genes (PER1, PER2, BMAL1, CRY1) were expressed in human heart tissue.
• PER1, PER2, and BMAL1 exhibited significant circadian rhythms, with distinct acrophases (peak times) in the morning and evening.
• CRY1 did not show a detectable circadian rhythm. Rhythmic patterns were consistent across all patient groups.
• Human myocardial clock gene staging was found to be in antiphase compared to rodents.

Conclusions:

• The human heart possesses robust circadian clock gene oscillations, particularly for PER1, PER2, and BMAL1.
• These myocardial circadian rhythms are more pronounced than in other human tissues.
• The timing of PER and BMAL1 rhythm peaks and troughs aligns with periods of increased myocardial events, suggesting a potential role in cardiovascular health.