Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases
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 microdo...
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doaj-6dae5bb93a484e878e4dd5e20e4ff5972020-11-25T03:46:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01217462746210.3390/ijms21207462Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular DiseasesMirna S. Sadek0Eleder Cachorro1Ali El-Armouche2Susanne Kämmerer3Department of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, GermanyDepartment of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, GermanyDepartment of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, GermanyDepartment of Pharmacology and Toxicology, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, GermanyPhosphodiesterases (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.https://www.mdpi.com/1422-0067/21/20/7462PDE2cAMP/cGMP crosstalknatriuretic peptidesNO signalingheart failurearrhythmia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mirna S. Sadek Eleder Cachorro Ali El-Armouche Susanne Kämmerer |
spellingShingle |
Mirna S. Sadek Eleder Cachorro Ali El-Armouche Susanne Kämmerer Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases International Journal of Molecular Sciences PDE2 cAMP/cGMP crosstalk natriuretic peptides NO signaling heart failure arrhythmia |
author_facet |
Mirna S. Sadek Eleder Cachorro Ali El-Armouche Susanne Kämmerer |
author_sort |
Mirna S. Sadek |
title |
Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases |
title_short |
Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases |
title_full |
Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases |
title_fullStr |
Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases |
title_full_unstemmed |
Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases |
title_sort |
therapeutic implications for pde2 and cgmp/camp mediated crosstalk in cardiovascular diseases |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-10-01 |
description |
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. |
topic |
PDE2 cAMP/cGMP crosstalk natriuretic peptides NO signaling heart failure arrhythmia |
url |
https://www.mdpi.com/1422-0067/21/20/7462 |
work_keys_str_mv |
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