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Calcineurin and human heart failure

Nature Medicine volume 5, pages 246–247 (1999)Cite this article

To the editor–Heart failure afflicts an estimated 4–5 million individuals in the United States each year at a cost of approximately $12 billion1,2. Of this group, a few hundred thousand have advanced heart failure, characterized by a 2-year mortality rate of greater than 90% (ref. 3). Many intracellular signaling pathways and second messenger systems are involved in cardiac hypertrophy and heart failure. One potential central molecule associated with cardiac hypertrophy and the progressive nature of heart failure is calcium. Intracellular calcium regulates myocardial contractility and relaxation by coordinated release and sequestration of calcium from the sarcolemma and sarcoplasmic reticulum. Heart failure is associated with increased intracellular basal calcium concentrations, decreased amplitude of the systolic calcium transient and defective sequestration of calcium in the sarcoplasmic reticulum during diastole4. These alterations in calcium handling are thought to play an essential part in the progressive deterioration of cardiac function in heart failure

Alterations in intracellular calcium handling associated with heart failure might also be expected to activate calcium-sensitive intracellular signaling factors, including PKC isoforms, MAPK signaling factors and calcineurin. Calcineurin, a calcium-regulated phosphatase, is sufficient to mediate cardiac hypertrophy in transgenic mouse hearts when overexpressed in an activated form5. Cyclosporin and FK506, both calcineurin inhibitors, can prevent cardiac hypertrophy and dilated myopathy in rodent models of heart disease6. Therefore, calcineurin may be important in cardiac reactive responses; however, it is uncertain whether these findings have relevance to human heart disease.

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References

  1. Levit, K.R., Lazenby, H.C. & Cown, C.A. National health expenditures, 1990. Health Care Finan. Rev. 13, 29–54 (1991).

    CAS  Google Scholar 

  2. O'Connell, J.B. & Bristow, M.R. Economic impact of heart failure in the United States: time for a different approach. J. Heart Lung Transplant. 13, S107– S112 (1994).

    CAS  PubMed  Google Scholar 

  3. Gheorghiade, M. et al. Current medical therapy for advanced heart failure. Am. Heart J. 135, S231–S248 (1998).

    Article  CAS  Google Scholar 

  4. Balke, C.W. & Shorofsky, S.R. Alterations in calcium handling in cardiac hypertrophy and heart failure. Cardiovasc. Res. 37, 290–299 (1998).

    Article  CAS  Google Scholar 

  5. Molkentin, J.D. et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93, 215– 228 (1998).

    Article  CAS  Google Scholar 

  6. Sussman, M.A. et al. Prevention of Cardiac Hypertrophy in Mice by Calcineurin Inhibition. Science 281, 1690– 1693 (1998).

    Article  CAS  Google Scholar 

  7. Dolmetsch, R.E., Lewis, R.S., Goodnow, C.C. & Healy, J.I. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386, 855– 858 (1997).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, 45229-3039, OH

    Hae W. Lim & Jeffery D. Molkentin

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  1. Hae W. Lim
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  2. Jeffery D. Molkentin
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Correspondence to Jeffery D. Molkentin.

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Lim, H., Molkentin, J. Calcineurin and human heart failure. Nat Med 5, 246–247 (1999). https://doi.org/10.1038/6430

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