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Suppression of physiological cardiomyocyte proliferation in the rat pup after neonatal glucocorticosteroid treatment

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Abstract

Background

Glucocorticosteroids (mostly dexamethasone) are widely used to prevent chronic lung disease in premature infants. Neonatal rats treated with dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a severely reduced life expectancy. In the present study we tested the hypothesis that a lower number of cardiomyocytes in later life is caused by a reduced cardiomyocyte proliferation and/or by early cell death (apoptosis).

Methods and results

Rat pups received dexamethasone or saline control on day 1, 2 and 3 and were sacrificed at day 0, 2, 4, 7 and 21. The cardiomyocytes of dexamethasone treated pups showed a reduced proliferation as indicated by a lower mitotic index and reduced number of Ki–67 positive cardiomyocytes on day 2 and 4 as compared to day 0 and day 7 and also as compared to the age–matched saline pups. On day 7 and day 21 the mitotic index was not different between groups. From day 2 onward up to day 21 dexamethasone treated pups showed a lower number of cardiomyocytes. The cardiomyocytes showed no signs (<<1%) of apoptosis (Caspase–3 and cleaved–PARP) in any group.

Conclusion

The temporary suppression of cardiomyocyte hyperplasia found in dexamethasone treated pups eventually leads to a reduced number and hypertrophy of cardiomyocytes during adult life.

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Abbreviations

Bw::

body weight

Dex::

dexamethasone

GC::

glucocorticosteroids

Hw::

heart weight

RDS::

(infant) respiratory distress syndrome

PARP::

poly(ADP–ribose)polymerase

Sal::

saline

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Authors and Affiliations

  1. Department of Neonatology, University Medical Center Utrecht, Wilhelmina Children’s Hospital Roomnr. KE.04.123.1, 85090, 3508 AB, Utrecht, The Netherlands

    W. B. de Vries MD, M. P. Bal MD, P. J. G. H. Kamphuis PhD & F. van Bel MD, PhD

  2. Department of Cardiology, Leiden University Medical Center, 9600, 2300 RC, Leiden, The Netherlands

    M. P. Bal MD, J. Baan PhD & P. Steendijk PhD

  3. Department of Pediatrics, University of Groningen Research Laboratory CMCV-2, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    M. P. Bal MD & F. R. van der Leij PhD

  4. Department of Pathology, University Medical Center Utrecht Roomnr. H.04.312, 85500, 3508 GA, Utrecht, The Netherlands

    P. Homoet-van der Kraak, R. A. de Weger PhD & M. F. M. van Oosterhout MD, PhD

Authors
  1. W. B. de Vries MD
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  2. M. P. Bal MD
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  3. P. Homoet-van der Kraak
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  4. P. J. G. H. Kamphuis PhD
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  5. F. R. van der Leij PhD
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  6. J. Baan PhD
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  7. P. Steendijk PhD
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  8. R. A. de Weger PhD
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  9. F. van Bel MD, PhD
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  10. M. F. M. van Oosterhout MD, PhD
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Corresponding author

Correspondence to F. van Bel MD, PhD.

Additional information

Supported by the Netherlands Heart Foundation (FvB grant NHS 2001B081)

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de Vries, W.B., Bal, M.P., Homoet-van der Kraak, P. et al. Suppression of physiological cardiomyocyte proliferation in the rat pup after neonatal glucocorticosteroid treatment. Basic Res Cardiol 101, 36–42 (2006). https://doi.org/10.1007/s00395-005-0557-0

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  • DOI: https://doi.org/10.1007/s00395-005-0557-0

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