0009 : Cardiac mitochondrial function is time-of-day dependent
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文摘
Many cardiovascular (patho) physiological processes follow a circadian pattern. Liver mitochondria function has recently been shown to be paced by circadian rhythms. Mitochondria play a key role in cardiomyocyte functions.

Aim To determine

whether mitochondrial oxidative phosphorylation, ROS production and calcium retention capacity (mCRC) are time-of-day dependent.

Methods and results

Wild-type mice were sacrificed at the wake-to-sleep or sleep-to-wake transition period. Cardiac mitochondrial function was explored using heart homogenate preparations. Oxidative phosphorylation coupling in presence of pyruvate and malate was estimated by the respiratory control ratios (RCR), calculated as the ratio between ADP-stimulated (state 3) and ADP-free (state 2) respiration. Despite the absence of differences in state 3 and state 2 respiration, RCR were significantly lower at the sleep-to-wake compared to the wake-to-sleep transition period (p = 0.04). Under conditions mimicking a pathological substrate environment, such as the one encountered during reperfusion, i.e. high level of succinate, presence of oxygen, absence of ADP and energy substrates, H2O2 production relative to oxygen consumption (H2O2/O2) was 18% higher (p=0.05) and mCRC significantly reduced (p=0.01) at the sleep-to-wake compared to the wake-to-sleep transition period.

Conclusion

Mitochondrial function exhibits a time-of-day dependence in mouse cardiomyocytes with poorer mitochondrial coupling, higher ROS production and reduced mCRC at the sleep-to-wake transition period. Cardiac mitochondria could therefore represent a relevant target to impact on the circadian pattern of cardiovascular diseases.

The author hereby declares no conflict of interest

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