title: Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective.
abstract: Cyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating multiple aspects of cardiac and vascular muscle functions. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families that 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 the myocardium and vascular smooth muscle, the PDE3 and PDE4 families predominate, degrading cAMP and thereby regulating cardiac excitation-contraction coupling and smooth muscle contractile tone. PDE3 inhibitors are positive inotropes and vasodilators in humans, but their use is limited to acute heart failure and intermittent claudication. PDE5 is particularly important for the degradation of cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. 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, as well as several vascular diseases. After a brief presentation of the cyclic nucleotide pathways in cardiac and vascular cells, and the major characteristics of the PDE superfamily, this review will focus on the current use of PDE inhibitors in cardiovascular diseases, and the recent research developments that could lead to better exploitation of the therapeutic potential of these enzymes in the future.
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bobin
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Milia
authors.initials: M
authors.lastname: Belacel-Ouari
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Bedioune
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leroy
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblais
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France. Electronic address: rodolphe.fischmeister@inserm.fr.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Fischmeister
authors.affiliation: UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France. Electronic address: gregoire.vandecasteele@u-psud.fr.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Vandecasteele
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases
keywords: AMPc; Cardiovascular diseases; Cyclic nucleotide phosphodiesterases; GMPc; Maladies cardiovasculaires; Phosphodiestérase des nucléotides cycliques; cAMP; cGMP