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Day/night rhythms in gene expression of the normal murine heart

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Abstract

Molecular circadian oscillators have recently been identified in heart and many other peripheral organs; however, little is known about the physiologic significance of circadian gene cycling in the periphery. While general temporal profiles of gene expression in the heart have been described under constant lighting conditions, patterns under normal day/night conditions may be distinctly different. To understand how gene expression contributes to cardiac function, especially in human beings, it is crucial to examine these patterns in 24-h light and dark environments. High-density oligonucleotide microarrays were used to assess myocardial expression of 12,488 murine genes at 3-h intervals under the normal conditions of light and dark cycling. Variation in genetic activity was considerable, as 1,634 genes (~13% of genes analyzed) exhibited statistically significant changes across the 24-h cycle. Some genes exhibited rhythmic expression, others showed abrupt change at light-to-dark and dark-to-light transitions. Importantly, genes that exhibited significant cycling rhythms mapped to key biological pathways, including for example cardiac cellular growth and remodeling, as well as transcription, translation, mitochondrial respiration, and signaling pathways. Gene expression in the heart is remarkably different in the day versus the night. Some gene cycling may be driven by the central circadian pacemaker, while other changes appear to be responses to light and dark. This has important implications regarding our understanding of how the molecular physiology of the heart is controlled, including temporal patterns of organ growth, renewal, and disease, comparative gene expression, and the most appropriate times for administration of therapy.

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Acknowledgements

We thank A. Dupuis for consulting on statistical analyses, E. Cuckerman for technical assistance, and D. Black and A. Wagner for graphics assistance. We are grateful for the support of the A. Ephriam and Shirley Diamond Cardiomyopathy Research Fund, and a grant from the Heart and Stroke Foundation of Ontario (T4479). D.D.B. acknowledges support from the Natural Science and Engineering Research Council of Canada. P.L. is Polo Chair of the Heart and Stroke Foundation of Ontario. M.S. acknowledges support from the University of Virginia for both the Center for Biomathematical Technology and the Center for Biological Timing, as well as NSF, NIH, and NSBRI.

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Authors and Affiliations

  1. Heart and Stroke Richard Lewar Centre of Excellence and Toronto General Hospital Research Institute, Toronto, Canada

    Tami Martino, Sara Arab, Nazneen Tata, Peter Liu, Maria Trivieri & Michael J. Sole

  2. Department of Physiology, University of Toronto, Toronto, Canada

    Denise D. Belsham & Fang Cai

  3. Departments of Psychology and Zoology, University of Toronto, Toronto, Canada

    Martin Ralph

  4. Department of Internal Medicine, Division of Endocrinology and Metabolism, The Center for Biomathematical Technology, University of Virginia Health System, Charlottesville, Virginia, USA

    Marty Straume

  5. 13-212a EN, Toronto General Hospital, Toronto, Ontario, M5G 2C4, Canada

    Michael J. Sole

Authors
  1. Tami Martino
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  2. Sara Arab
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  3. Marty Straume
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  4. Denise D. Belsham
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  5. Nazneen Tata
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  6. Fang Cai
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  7. Peter Liu
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  8. Maria Trivieri
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  9. Martin Ralph
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  10. Michael J. Sole
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Corresponding author

Correspondence to Michael J. Sole.

Additional information

T. Martino and S. Arab contributed equally to this study

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Martino, T., Arab, S., Straume, M. et al. Day/night rhythms in gene expression of the normal murine heart. J Mol Med 82, 256–264 (2004). https://doi.org/10.1007/s00109-003-0520-1

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  • DOI: https://doi.org/10.1007/s00109-003-0520-1

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