Cyclic nucleotide imaging and cardiovascular disease

Berisha, Filip; Nikolaev, Viacheslav O.

doi:10.1016/j.pharmthera.2017.02.038

Cited by 18 publications

(9 citation statements)

References 115 publications

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“…SICM is a non-optical imaging technique that uses a small glass nanopipette to obtain a highly resolved morphological profile of a living cell membrane based on ion current measurement [ 147 , 148 , 149 , 150 ]. It can also be combined with FRET for more accurate and specific detection of microdomain alterations in health and disease [ 149 , 151 , 152 ].…”

Section: Visualization Of Compartmentalized Camp and Cgmpmentioning

confidence: 99%

Imaging of PDE2- and PDE3-Mediated cGMP-to-cAMP Cross-Talk in Cardiomyocytes

Pavlaki

Nikolaev

2018

JCDD

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Cyclic nucleotides 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP) are important second messengers that regulate cardiovascular function and disease by acting in discrete subcellular microdomains. Signaling compartmentation at these locations is often regulated by phosphodiesterases (PDEs). Some PDEs are also involved in the cross-talk between the two second messengers. The purpose of this review is to summarize and highlight recent findings about the role of PDE2 and PDE3 in cardiomyocyte cyclic nucleotide compartmentation and visualization of this process using live cell imaging techniques.

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Section: Visualization Of Compartmentalized Camp and Cgmpmentioning

confidence: 99%

Imaging of PDE2- and PDE3-Mediated cGMP-to-cAMP Cross-Talk in Cardiomyocytes

Pavlaki

Nikolaev

2018

JCDD

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“…Dysregulation of local cAMP signaling is associated with cardiovascular diseases, e.g., maladaptive cardiac remodeling and heart failure [ 116 , 117 ]. FRET-based imaging using genetically encoded sensors (cAMP-binding and PKA activity reporters) is utilized to visualize local cAMP signaling components and real-time changes in cAMP levels with high spatio-temporal resolution [ 118 , 119 , 120 , 121 ]. Such sensors can be targeted to various subcellular locations including in cardiac myocytes in close proximity of sarcolemmal ion channels and SR proteins involved in Ca 2+ handling, e.g., RyR 2 and SERCA2a [ 122 , 123 , 124 , 125 ].…”

Section: A-kinase Anchoring Proteins (Akaps)mentioning

confidence: 99%

Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

Ercu

Klussmann

2018

JCDD

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A-kinase anchoring proteins (AKAPs) and cyclic nucleotide phosphodiesterases (PDEs) are essential enzymes in the cyclic adenosine 3′-5′ monophosphate (cAMP) signaling cascade. They establish local cAMP pools by controlling the intensity, duration and compartmentalization of cyclic nucleotide-dependent signaling. Various members of the AKAP and PDE families are expressed in the cardiovascular system and direct important processes maintaining homeostatic functioning of the heart and vasculature, e.g., the endothelial barrier function and excitation-contraction coupling. Dysregulation of AKAP and PDE function is associated with pathophysiological conditions in the cardiovascular system including heart failure, hypertension and atherosclerosis. A number of diseases, including autosomal dominant hypertension with brachydactyly (HTNB) and type I long-QT syndrome (LQT1), result from mutations in genes encoding for distinct members of the two classes of enzymes. This review provides an overview over the AKAPs and PDEs relevant for cAMP compartmentalization in the heart and vasculature and discusses their pathophysiological role as well as highlights the potential benefits of targeting these proteins and their protein-protein interactions for the treatment of cardiovascular diseases.

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“…Pathological redistribution of compartmentalized cellular components modulating cyclic nucleotide secondary messenger signalling are increasingly being reported to prompt pathways associated with adverse cardiac remodeling [ 7 , 8 , 9 ]. Many researchers have therefore focused to investigate compartmentalized microdomain signalling and established multiple indispensable novel technology platforms to examine complex signalling microcompartments [ 10 , 11 , 12 ]. Development of cardiac and vascular microdomain specific therapeutics may potentially offer a breakthrough in CVD therapy by limiting pathological signalling and remodeling mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

Sadek

Cachorro

El‐Armouche

et al. 2020

IJMS

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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.

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Cyclic nucleotide imaging and cardiovascular disease

Cited by 18 publications

References 115 publications

Imaging of PDE2- and PDE3-Mediated cGMP-to-cAMP Cross-Talk in Cardiomyocytes

Imaging of PDE2- and PDE3-Mediated cGMP-to-cAMP Cross-Talk in Cardiomyocytes

Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

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