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Cardiac development

Transcription and the broken heart

Nature volume 392, pages 129–130 (1998)Cite this article

Congenital heart defects occur in an astonishing 1% of live births1,2, and fetal heart malformations are implicated in many pregnancies that end in stillbirth or spontaneous abortion2. Why, of all the body's complex organ systems, is the heart so susceptible to malformation during fetal development? Genetic factors are probably central to many congenital heart defects, but complicating factors such as environmental toxins or the diet and age of the parents are likely to affect the severity of these disorders. Despite compelling statistics on their incidence, and in the face of exciting genetic progress3,4 implicating several genes in the developmental programme of the normal heart, we still do not understand biochemically why heart defects are so prevalent. This is mainly due to a lack of the molecular targets that might indicate preventative therapeutic approaches or outline signalling systems for further investigation.

The ventricular septal structure, which separates the left and right ventricles, was also rendered defective by the mutations. Less severely affected (although clearly defective in the study of de la Pompa et al.), were the tricuspid and mitral valves, which regulate the flow of blood from the right and left atria into their respective ventricles. The spectrum of malformations found in human hearts more closely resembles the defects seen in the pulmonary and aortic valves of the mouse NF-ATc mutants. Human clinical cases only rarely involve the complete lack of all four valves, consistent with the phenotypes observed in the mice. However, as a result of these combined defects observed in both studies5,6, the mouse embryos died after 14-15 days' gestation.

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Figure 1: Cardiac valves that depend on the activity of fetal NF-ATc.
Figure 2: Common paths for activation of NF-ATc in T cells and fetal endocardial cells?a, T-cell activation involving.

References

  1. Ferencz, C. et al. Am. J. Epidemiol. 121, 31–36 (1985).

    Google Scholar 

  2. Hoffman, J. I. E. Pediatr. Cardiol. 16, 155–165 (1995).

    Google Scholar 

  3. Rossant, J. Circulation Res. 78, 349–353 (1996).

    Google Scholar 

  4. Olsen, E. N. & Srivastava, D. Science 272, 671–676 (1996).

    Google Scholar 

  5. de la Pompa, J. et al. Nature 392, 182–186 (1998).

    Article  ADS  CAS  Google Scholar 

  6. Ranger, A. M. et al. Nature 392, 186–190 (1998).

    Article  ADS  CAS  Google Scholar 

  7. Rao, A., Luo, C. & Hogan, P. G. Annu. Rev. Immunol. 15, 707–747 (1997).

    Google Scholar 

  8. Nolan, G. P. Cell 77, 795–798 (1994).

    Google Scholar 

  9. Xanthoudakis, S. et al. Science 272, 892–895 (1996).

    Google Scholar 

Download references

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  1. the Department of Molecular Pharmacology and the Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Garry P. Nolan

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  1. Garry P. Nolan
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Nolan, G. Transcription and the broken heart. Nature 392, 129–130 (1998). https://doi.org/10.1038/32290

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