Neonatal rat cardiomyocytes as an in vitro model for circadian rhythms in the heart

TY - JOUR

T1 - Neonatal rat cardiomyocytes as an in vitro model for circadian rhythms in the heart

AU - du Pré, Bastiaan C

AU - Dierickx, Pieterjan

AU - Crnko, Sandra

AU - Doevendans, Pieter A

AU - Vos, Marc A

AU - Geijsen, Niels

AU - Neutel, Didi

AU - van Veen, Toon A B

AU - van Laake, Linda W

N1 - Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2017/11

Y1 - 2017/11

N2 - Circadian rhythms are biorhythms with a 24-hour period that are regulated by molecular clocks. Several clinical and animal models have been developed to analyze the role of these rhythms in cardiovascular physiology, disease and therapy, but a convenient in vitro model that mimics both molecular and functional circadian effects of the heart is not available. Therefore, we established a neonatal rat cardiomyocyte model that recapitulates in vivo circadian rhythmicity, as measured by anti-phasic oscillatory mRNA expression of two core clock genes, Bmal1 and Per2 and that shows functional dependence on the clock as indicated by an oscillating response in apoptosis induced by doxorubicin, hydroperoxide or hypoxia. In addition, perturbation of the cardiac clock by the use of several compounds including Resveratrol and Ex-527 was found to result in loss of functional rhythmicity. This indicates that neonatal rat cardiomyocytes are a good model to investigate the cardiac circadian clock as well as a system that allows for fast and easy preclinical testing of the influence of compounds on circadian rhythmicity that might have crucial effects on cardiac health.

AB - Circadian rhythms are biorhythms with a 24-hour period that are regulated by molecular clocks. Several clinical and animal models have been developed to analyze the role of these rhythms in cardiovascular physiology, disease and therapy, but a convenient in vitro model that mimics both molecular and functional circadian effects of the heart is not available. Therefore, we established a neonatal rat cardiomyocyte model that recapitulates in vivo circadian rhythmicity, as measured by anti-phasic oscillatory mRNA expression of two core clock genes, Bmal1 and Per2 and that shows functional dependence on the clock as indicated by an oscillating response in apoptosis induced by doxorubicin, hydroperoxide or hypoxia. In addition, perturbation of the cardiac clock by the use of several compounds including Resveratrol and Ex-527 was found to result in loss of functional rhythmicity. This indicates that neonatal rat cardiomyocytes are a good model to investigate the cardiac circadian clock as well as a system that allows for fast and easy preclinical testing of the influence of compounds on circadian rhythmicity that might have crucial effects on cardiac health.

KW - Journal Article

U2 - 10.1016/j.yjmcc.2017.08.009

DO - 10.1016/j.yjmcc.2017.08.009

M3 - Article

C2 - 28823816

SN - 0022-2828

VL - 112

SP - 58

EP - 63

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

ER -