Various Regulatory Modes for Circadian Rhythmicity and Sexual Dimorphism in the Non-Neuronal Cardiac Cholinergic System

Journal of Cardiovascular Translational Research
Shino OikawaYoshihiko Kakinuma

Abstract

Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS) regulated by a positive feedback system; however, its other regulatory mechanisms remain to be elucidated, which include the epigenetic control or regulation by the female sex steroid, estrogen. Here, the NNCCS was shown to possess a circadian rhythm; its activity was upregulated in the light-off phase via histone acetyltransferase (HAT) activity and downregulated in the light-on phase. Disrupting the circadian rhythm altered the physiological choline acetyltransferase (ChAT) expression pattern. The NNCCS circadian rhythm may be regulated by miR-345, independently of HAT, causing decreased cardiac ChAT expression. Murine cardiac ChAT expression and ACh contents were increased more in female hearts than in male hearts. This upregulation was downregulated by treatment with the estrogen receptor antagonist tamoxifen, and in contrast, estrogen reciprocally regulated cardiac miR-345 expression. These results suggest that the NNCCS is regulated by the circadian rhythm and is affected by sexual dimorphism.

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Citations

Jan 20, 2021·The Journal of Physiological Sciences : JPS·Shino OikawaYoshihiko Kakinuma
Dec 3, 2020·American Journal of Physiology. Cell Physiology·Cibele Rocha-ResendeSilvia Guatimosim
Jan 13, 2021·International Journal of Molecular Sciences·Yoshihiko Kakinuma
Apr 23, 2021·Acta Physiologica·Gisele L CavalcanteJoão Paulo J Sabino

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