The circadian clock influences heart performance

Area of Science:

• Cardiovascular Physiology
• Chronobiology
• Molecular Biology

Background:

• Circadian rhythms anticipate daily environmental changes, optimizing physiological responses.
• Disrupted circadian rhythms impact various bodily functions, but their role in heart performance is unclear.
• The circadian clock's influence on cardiac function, especially in anticipation of workload, requires investigation.

Purpose of the Study:

• To investigate the role of the circadian clock in regulating heart performance.
• To determine if cardiac function exhibits diurnal variations and responds to exercise in a time-dependent manner.
• To explore the impact of circadian clock disruption and PGC1α overexpression on cardiac function and associated metabolic pathways.

Main Methods:

• Noninvasive, real-time echocardiography was used to monitor heart function and structure in mice.
• Diurnal variations in ejection fraction (EF) and shortening fraction (FS) were assessed in wild-type and mutant mice.
• The effects of forced exercise and imposed light regimens on cardiac function were evaluated.
• Gene expression changes, including clock genes, PGC1α, PPARα, GLUT4, and ACSL1, were analyzed.

Main Results:

• Wild-type mice exhibited diurnal variations in EF and FS, which increased with forced exercise.
• Circadian clock gene disruption and imposed light regimens altered diurnal EF and FS variations.
• Overexpression of PGC1α inhibited clock gene expression and decreased PPARα, GLUT4, and ACSL1 expression.
• PGC1α overexpression abolished the diurnal variation of EF, suggesting a link to metabolic gene regulation.

Conclusions:

• The circadian clock plays a crucial role in anticipating daily workload and regulating cardiac function.
• Disruptions in circadian rhythms, particularly through PGC1α, impair cardiac function and diurnal adaptations.
• PGC1α may mediate circadian-controlled cardiac dysfunction by influencing the rhythmic expression of metabolic genes.