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The role of clock genes and circadian rhythm in the development of cardiovascular diseases

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Abstract

The time of onset of cardiovascular disorders such as myocardial infarctions or ventricular arrhythmias exhibits a circadian rhythm. Diurnal variations in autonomic nervous activity, plasma cortisol level or renin–angiotensin activity underlie the pathogenesis of cardiovascular diseases. Transcriptional–translational feedback loop of the clock genes constitute a molecular clock system. In addition to the central clock in the suprachiasmatic nucleus, clock genes are also expressed in a circadian fashion in each organ to make up the peripheral clock. The peripheral clock seems to be beneficial for anticipating external stimuli and thus contributes to the maintenance of organ homeostasis. Loss of synchronization between the central and peripheral clocks also augments disease progression. Moreover, accumulating evidence shows that clock genes affect inflammatory and intracellular metabolic signaling. Elucidating the roles of the molecular clock in cardiovascular pathology through the identification of clock controlled genes will help to establish a novel therapeutic approach for cardiovascular disorders.

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Abbreviations

CCG:

Clock-controlled gene

SCN:

Suprachiasmatic nucleus

ANP:

Atrial natriuretic peptide

PAR:

Proline and acid-rich

LV:

Left ventricle

MI:

Myocardial infarction

L/D:

Light/dark

TAC:

Transverse aortic constriction

CCM:

Cardiomyocyte-specific clock mutant

NO:

Nitric oxide

eNOS:

Endothelial NO synthase

PAI-1:

Plasminogen activator inhibitor-1

VT/VF:

Ventricular tachycardia/fibrillation

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, Japan (to K.M. and N.T. 25461113).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Norihiko Takeda

  2. Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Koji Maemura

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Correspondence to Norihiko Takeda or Koji Maemura.

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Takeda, N., Maemura, K. The role of clock genes and circadian rhythm in the development of cardiovascular diseases. Cell. Mol. Life Sci. 72, 3225–3234 (2015). https://doi.org/10.1007/s00018-015-1923-1

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