Cyclic Nucleotide Phosphodiesterases and Compartmentation in Normal and Diseased Heart

  • Ibrahim Bedioune
  • Pierre Bobin
  • Jérôme Leroy
  • Rodolphe FischmeisterEmail author
  • Grégoire VandecasteeleEmail author
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol., volume 3)


Cyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cAMP and cGMP, thereby regulating multiple aspects of cardiac function. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families which are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP controlling specific cell functions in response to various neurohormonal stimuli. In myocardium, the PDE3 and PDE4 families are predominant to degrade cAMP and thereby regulate cardiac excitation-contraction coupling. PDE3 inhibitors are positive inotropes and vasodilators in human, but their use is limited to acute heart failure and intermittent claudication. PDE5 is particularly important to degrade cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. However, these drugs do not seem efficient in heart failure with preserved ejection fraction. There is experimental evidence that these PDEs as well as other PDE families including PDE1, PDE2 and PDE9 may play important roles in cardiac diseases such as hypertrophy and heart failure. After a brief presentation of the cyclic nucleotide pathways in cardiac cells and the major characteristics of the PDE superfamily, this chapter will present their role in cyclic nucleotide compartmentation and the current use of PDE inhibitors in cardiac diseases together with the recent research progresses that could lead to a better exploitation of the therapeutic potential of these enzymes in the future.


cAMP cGMP Cyclic nucleotide phosphodiesterases Heart failure 



Adenylyl cyclases


A-kinase anchoring protein


Atrial natriuretic peptide


Brain natriuretic peptide




Ca2+/calmodulin-dependent kinase II


Cyclic adenosine monophosphate


Cyclic guanosine monophosphate


Cyclic nucleotides


C-type natriuretic peptide


Excitation-contraction coupling


Exchange protein directly activated by cAMP


Extracellular signal-regulated kinase


Förster resonance energy transfer


cGMP-stimulated phosphodiesterases, Anabaena adenylyl cyclases, Fhla transcription factor


Guanylyl cyclase


Heart failure


Inducible-cAMP early repressor






L-type Ca2+ channels


Muscle AKAP


Nitric oxide


NO synthase


Cyclic nucleotide phosphodiesterase


Particulate guanylyl cyclase




Phosphoinositide 3-kinase, γ isoform


cAMP-dependent protein kinase


cGMP-dependent protein kinase




Ryanodine receptor type 2


Sarco-endoplasmic reticulum Ca2+-ATPase


Soluble guanylyl cyclase


Sarcoplasmic reticulum


Troponin I


β-adrenergic receptors



This work was supported by the Fondation de France (to GV) and the Agence Nationale de la Recherche 2010 BLAN 1139-01 (to GV). PB and IB were supported by PhD fellowships from the region Ile-de-France (CORDDIM) and Fondation pour la Recherche Médicale.

Compliance with Ethical Standards

Conflict of Interest



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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Ibrahim Bedioune
    • 1
  • Pierre Bobin
    • 1
  • Jérôme Leroy
    • 1
  • Rodolphe Fischmeister
    • 1
    Email author
  • Grégoire Vandecasteele
    • 1
    Email author
  1. 1.Faculté de PharmacieInserm, UMR-S 1180, Univ. Paris-Sud, Université Paris-SaclayChâtenay-MalabryFrance

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