Heart Failure pp 249-269 | Cite as

Cardiac Phosphodiesterases and Their Modulation for Treating Heart Disease

  • Grace E. Kim
  • David A. KassEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 243)


An important hallmark of cardiac failure is abnormal second messenger signaling due to impaired synthesis and catabolism of cyclic adenosine 3′,5′- monophosphate (cAMP) and cyclic guanosine 3′,5′- monophosphate (cGMP). Their dysregulation, altered intracellular targeting, and blunted responsiveness to stimulating pathways all contribute to pathological remodeling, muscle dysfunction, reduced cell survival and metabolism, and other abnormalities. Therapeutic enhancement of either cyclic nucleotides can be achieved by stimulating their synthesis and/or by suppressing members of the family of cyclic nucleotide phosphodiesterases (PDEs). The heart expresses seven of the eleven major PDE subtypes – PDE1, 2, 3, 4, 5, 8, and 9. Their differential control over cAMP and cGMP signaling in various cell types, including cardiomyocytes, provides intriguing therapeutic opportunities to counter heart disease. This review examines the roles of these PDEs in the failing and hypertrophied heart and summarizes experimental and clinical data that have explored the utility of targeted PDE inhibition.


Cyclic nucleotides Heart failure Myocardium Phosphodiesterases Protein kinase A Protein kinase G 


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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Division of Cardiology, Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Pharmacology and Molecular SciencesJohns Hopkins University School of MedicineBaltimoreUSA

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