Impact of light-dark cycle on the expression of circadian clock genes, electrocardiography, and myocardial function in mice

Abstract

Background: The light-dark (LD) cycle regulates circadian rhythms that influence cardiac function and autonomic regulation. However, the impact of LD cycle disturbances on cardiac electrophysiology and gene expression remains unclear. This study investigated how disrupted light exposure affects cardiac rhythm, function, and gene expression in mice.

Methods: Eight-week-old C57BL/6 J mice were exposed to either a normal LD cycle (12 h light/12 h dark, NLD) or a disrupted LD cycle (24 h light for 3 days/24 h dark for 4 days, DLD) for 12 and 24 weeks. Monthly electrocardiographic (ECG) and echocardiographic assessments were performed. Gene expression related to circadian regulation, mitochondrial function, and cardiac remodeling was analyzed.

Results: DLD mice exhibited transient weight gain and persistent cardiac hypertrophy. ECG analysis showed shortened RR intervals, prolonged QTc intervals (weeks 4 and 8), and widened QRS duration (week 16). Heart rate variability analysis indicated sustained sympathovagal imbalance (increased LF/HF ratio). Echocardiography revealed early cardiac remodeling with increased left ventricular outflow tract velocity, pressure gradient, and internal diameter. Gene analysis showed early Per2 and Nr1d1 dysregulation, followed by Bmal1, Clock, Rora, and Rorc downregulation and Nr1d1 upregulation at 24 weeks. Mitochondrial dysfunction, fibrosis, and inflammation markers were also dysregulated.

Conclusion: Chronic LD disruption leads to circadian misalignment, autonomic imbalance, and cardiac remodeling, potentially contributing to adverse cardiovascular outcomes.

Translational relevance: This model simulates circadian disruption in shift workers and individuals with irregular sleep patterns, highlighting prolonged circadian misalignment may elevate cardiovascular risk and the importance of circadian health in cardiovascular prevention strategies.

Keywords: Circadian clock disruption; Echocardiography; Electrocardiography (ECG); Light-dark (LD) cycle; Mitochondrial function.