Cardiac phosphodiesterases and their modulation for treating heart disease

Grace E. Kim, David A Kass

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish (US)
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages249-269
Number of pages21
Volume243
DOIs
StatePublished - 2017

Publication series

NameHandbook of Experimental Pharmacology
Volume243
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Kim, G. E., & Kass, D. A. (2017). Cardiac phosphodiesterases and their modulation for treating heart disease. In Handbook of Experimental Pharmacology (Vol. 243, pp. 249-269). (Handbook of Experimental Pharmacology; Vol. 243). Springer New York LLC. https://doi.org/10.1007/164_2016_82