Disrupting the heart muscle’s internal clock affects its contraction, metabolism, and gene activity

At 12 weeks of age, cardiomyocyte-specific circadian clock mutant (CCM) mice exhibit bradycardia and altered heart rate variations.

• CCM mice show attenuation of diurnal variations in heart rate without conduction system abnormalities.
• In CCM hearts, reduced heart rate persists even when perfused ex vivo, indicating an intrinsic phenomenon.
• Wild-type hearts demonstrate significant diurnal variations in response to increased workload, unlike CCM hearts.
• CCM hearts have increased myocardial oxygen consumption and fatty acid oxidation rates, but decreased cardiac efficiency.
• No changes in mitochondrial content or structure were observed in CCM hearts, but modest mitochondrial dysfunction was noted.
• Gene expression analysis revealed that 548 atrial and 176 ventricular genes had altered diurnal expression patterns in CCM mice.

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