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Locating heart failure

Nature Medicine volume 11, pages 1284–1285 (2005)Cite this article

Local levels of cAMP regulate the precise opening of the ryanodine receptor complex—which releases calcium at the start of a heartbeat. Loss or inhibition of phosphodiesterase 4D enzymatic activity leads to calcium leak, heart failure and arrhythmia.

Heart failure, the progressive loss of cardiac contractile performance, afflicts an estimated 5 million Americans1. Heart failure is associated with a profound alteration in calcium regulation and a reduction in β-adrenergic receptor signaling. As a result of these alterations, cardiac contractile reserve is essentially lost, and the risk of arrhythmia and sudden death increases2.

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Figure 1: Loss of PDE4 activity increases calcium flow through the ryanodine receptor.

Katie Ris

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  1. Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, 45229, Ohio, USA

    Jeffery D Molkentin

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  1. Jeffery D Molkentin
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Molkentin, J. Locating heart failure. Nat Med 11, 1284–1285 (2005). https://doi.org/10.1038/nm1205-1284

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  • DOI: https://doi.org/10.1038/nm1205-1284

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