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Genomic circuits and the integrative biology of cardiac diseases

Nature volume 407, pages 227–232 (2000)Cite this article

Abstract

Human cardiac disease is the result of complex interactions between genetic susceptibility and environmental stress. The challenge is to identify modifiers of disease, and to design new therapeutic strategies to interrupt the underlying disease pathways. The availability of genomic databases for many species is uncovering networks of conserved cardiac-specific genes within given physiological pathways. A new classification of human cardiac diseases can be envisaged based on the disruption of integrated genomic circuits that control heart morphogenesis, myocyte survival, biomechanical stress responses, cardiac contractility and electrical conduction.

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Figure 1: Cardiac neural crest defects.
Figure 2: Genetic modifiers and pathways for dilated cardiomyopathy.
Figure 3: Calcium cycling pathways in a cardiomyocyte and their involvement in heart failure.
Figure 4: A genetic pathway for cardiac sudden death as a result of defects in the transition between ventricular myocytes and conduction system cells (Purkinje fibre).

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Acknowledgements

I thank T. Nakamura, M. Hoshijima and S. Minamisawa for assistance with the figures, and J. Chen, S. Evans and K. Knowlton for helpful discussions. The author's laboratory is supported by grants from NIH, the Jean LeDucq Foundation, and an Endowed Chair from the American Heart Association (California Affiliate).

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  1. UCSD-Salk Program in Molecular Medicine and the UCSD Institute of Molecular Medicine, La Jolla, 92093, California, USA

    Kenneth R. Chien

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Correspondence to Kenneth R. Chien.

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Chien, K. Genomic circuits and the integrative biology of cardiac diseases. Nature 407, 227–232 (2000). https://doi.org/10.1038/35025196

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