Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.
Animals
Cardiovascular Diseases
/ diagnosis
Cardiovascular System
/ metabolism
Cyclic AMP
/ metabolism
Cyclic GMP
/ metabolism
Cyclic Nucleotide Phosphodiesterases, Type 2
/ metabolism
Fibroblasts
Humans
Myocytes, Cardiac
/ metabolism
Neurons
Nitric Oxide
/ metabolism
Second Messenger Systems
Signal Transduction
NO signaling
PDE2
arrhythmia
cAMP/cGMP crosstalk
cardiovascular disease
heart failure
inflammation
natriuretic peptides
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
10 Oct 2020
10 Oct 2020
Historique:
received:
02
09
2020
revised:
07
10
2020
accepted:
08
10
2020
entrez:
14
10
2020
pubmed:
15
10
2020
medline:
2
3
2021
Statut:
epublish
Résumé
Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3',5'-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases (CVDs). PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signaling with cardioprotective cGMP signaling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2- mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.
Identifiants
pubmed: 33050419
pii: ijms21207462
doi: 10.3390/ijms21207462
pmc: PMC7590001
pii:
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Cyclic AMP
E0399OZS9N
Cyclic Nucleotide Phosphodiesterases, Type 2
EC 3.1.4.17
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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