Viacheslav O. Nikolaev
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View article: An intracellular recombinant single‐chain variable antibody fragment as a new class of phosphodiesterase type 5 inhibitors
An intracellular recombinant single‐chain variable antibody fragment as a new class of phosphodiesterase type 5 inhibitors Open
Background and Purpose Cyclic guanosine monophosphate (cGMP) is a ubiquitous second messenger involved in human (patho‐)physiology. Phosphodiesterase 5 (PDE5) is a major cGMP hydrolyzing enzyme in many cell types including vascular smooth …
View article: Activated CaMKIIδ translocates to the RyR nanodomain in cardiomyocytes
Activated CaMKIIδ translocates to the RyR nanodomain in cardiomyocytes Open
Aims The heartbeat is triggered by the coordinated release of Ca2+ from the ryanodine receptor type-2 (RyR) in cardiomyocytes. Phosphorylation of RyR by Ca2+/calmodulin-dependent kinase IIδ (CaMKIIδ) fine-tunes this process in health, whil…
View article: New biosensors and transgenic mice for multiplex cGMP imaging
New biosensors and transgenic mice for multiplex cGMP imaging Open
Background and Purpose Cyclic guanosine monophosphate (cGMP) is a versatile second messenger that is important for human (patho‐)physiology and pharmacotherapy. Live‐cell imaging of cGMP with biosensors allows to elucidate its spatiotempor…
View article: Tracking antigen-specific T cell responses in patients with myocardial infarction
Tracking antigen-specific T cell responses in patients with myocardial infarction Open
Antigen-specific T cells can impact myocardial diseases, but appropriate model antigens and tools to track specific cells in patients are still lacking. Herein, we sought to identify and functionally characterize specific TCRs recognizing …
View article: RBM20-variants induce distinct calcium handling and metabolic phenotypes in patient-specific stem cell models of dilated and non-compaction cardiomyopathy
RBM20-variants induce distinct calcium handling and metabolic phenotypes in patient-specific stem cell models of dilated and non-compaction cardiomyopathy Open
Background and aim Mutations in the splice regulator RBM20 account for ∼3 % of genetic cardiomyopathies. In particular, the highly conserved RS domain is a hotspot for disease-associated mutations. Previously, mutations at same amino acid …
View article: Live Cell Monitoring of Phosphodiesterase Inhibition by Sulfonylurea Drugs
Live Cell Monitoring of Phosphodiesterase Inhibition by Sulfonylurea Drugs Open
Sulfonylureas (SUs) are a class of antidiabetic drugs widely used in the management of diabetes mellitus type 2. They promote insulin secretion by inhibiting the ATP-sensitive potassium channel in pancreatic β-cells. Recently, the exchange…
View article: Slack K+ channels confer protection against myocardial ischaemia/reperfusion injury
Slack K+ channels confer protection against myocardial ischaemia/reperfusion injury Open
Aims Na+-activated Slack potassium (K+) channels are increasingly recognized as regulators of neuronal activity, yet little is known about their role in the cardiovascular system. Slack activity increases when intracellular Na+ concentrati…
View article: The role of compartmentalized <scp>β‐AR</scp>/<scp>cAMP</scp> signaling in the regulation of lipolysis in white and brown adipocytes
The role of compartmentalized <span>β‐AR</span>/<span>cAMP</span> signaling in the regulation of lipolysis in white and brown adipocytes Open
White and brown adipocytes are central mediators of lipid metabolism and thermogenesis, respectively. Their function is tightly regulated by all three β‐adrenergic receptor (β‐AR) subtypes which are coupled to the production of the second …
View article: Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases
Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases Open
Flavonoid aglycones are secondary plant metabolites that exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and antiplatelet effects. However, the precise molecular mechanisms unde…
View article: Regulation of cardiac contractility and hypertrophy by cGMP nanodomains
Regulation of cardiac contractility and hypertrophy by cGMP nanodomains Open
cGMP is critically involved in the regulation of multiple intracellular events in cardiomyocytes which are crucial for both normal function and disease such as heart failure. Phosphodiesterases (PDEs), as the enzymes which degrade cyclic n…
View article: Antiplatelet effects of flavonoid aglycones on platelet activation are mediated by inhibition of phosphodiesterases
Antiplatelet effects of flavonoid aglycones on platelet activation are mediated by inhibition of phosphodiesterases Open
Flavonoids are a group of polyphenolic compounds found in different plants. Considered safe with favorable pharmacological effects and a wide therapeutic window, flavonoids emerge as promising candidates for medical application, including …
View article: Phosphodiesterases 4B and 4D Differentially Regulate cAMP Signaling in Calcium Handling Microdomains of Mouse Hearts
Phosphodiesterases 4B and 4D Differentially Regulate cAMP Signaling in Calcium Handling Microdomains of Mouse Hearts Open
The ubiquitous second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling (ECC) by signaling in discrete subcellular microdomains. Phosphodiesterase subfamilies 4B and 4D are critically i…
View article: A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation
A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation Open
T-cell activation is a pivotal process of the adaptive immune response with 3′,5′-cyclic adenosine monophosphate (cAMP) as a key regulator of T-cell activation and function. It governs crucial control over T-cell differentiation and produc…
View article: Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes
Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes Open
Aims Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reti…
View article: Role of Phosphodiesterase 1 in the Regulation of Real-Time cGMP Levels and Contractility in Adult Mouse Cardiomyocytes
Role of Phosphodiesterase 1 in the Regulation of Real-Time cGMP Levels and Contractility in Adult Mouse Cardiomyocytes Open
In mouse cardiomyocytes, the expression of two subfamilies of the calcium/calmodulin-regulated cyclic nucleotide phosphodiesterase 1 (PDE1)—PDE1A and PDE1C—has been reported. PDE1C was found to be the major subfamily in the human heart. It…
View article: A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing
A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing Open
Butyrophilin (BTN)–3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg s…
View article: Multimodal characterization of dilated cardiomyopathy: Geno‐ And Phenotyping of PrImary Cardiomyopathy (GrAPHIC)
Multimodal characterization of dilated cardiomyopathy: Geno‐ And Phenotyping of PrImary Cardiomyopathy (GrAPHIC) Open
Aims Cardiomyopathies (CMPs) are a heterogeneous group of diseases that are defined by structural and functional abnormalities of the cardiac muscle. Dilated cardiomyopathy (DCM), the most common CMP, is defined by left ventricular dilatio…
View article: From cells to circulating biomarker: BMP10 is a myocyte-secreted peptide with potential to detect atrial fibrillation
From cells to circulating biomarker: BMP10 is a myocyte-secreted peptide with potential to detect atrial fibrillation Open
Background Early onset detection and recurrence prediction of atrial fibrillation (AF) may improve therapeutic decision-making, prognosis and long-term outcome. Plasma proteome analyses and mechanistic studies identified bone morphogenetic…
View article: Microtubule-Mediated Regulation of β <sub>2</sub> AR Translation and Function in Failing Hearts
Microtubule-Mediated Regulation of β <sub>2</sub> AR Translation and Function in Failing Hearts Open
Background: β 1 AR (beta-1 adrenergic receptor) and β 2 AR (beta-2 adrenergic receptor)-mediated cyclic adenosine monophosphate signaling has distinct effects on cardiac function and heart failure progression. However, the mechanism regula…
View article: Regulation of the renin-angiotensin-aldosterone system by cyclic nucleotides and phosphodiesterases
Regulation of the renin-angiotensin-aldosterone system by cyclic nucleotides and phosphodiesterases Open
The renin-angiotensin-aldosterone system (RAAS) is one of the key players in the regulation of blood volume and blood pressure. Dysfunction of this system is connected with cardiovascular and renal diseases. Regulation of RAAS is under the…
View article: CRISPR/Cas9 Knock-Out in Primary Neonatal and Adult Cardiomyocytes Reveals Distinct cAMP Dynamics Regulation by Various PDE2A and PDE3A Isoforms
CRISPR/Cas9 Knock-Out in Primary Neonatal and Adult Cardiomyocytes Reveals Distinct cAMP Dynamics Regulation by Various PDE2A and PDE3A Isoforms Open
Cyclic nucleotide phosphodiesterases 2A (PDE2A) and PDE3A play an important role in the regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-to-cAMP crosstalk. Each of these PDEs has up to three dis…
View article: Live-cell imaging identifies cAMP microdomains regulating β-adrenoceptor-subtype-specific lipolytic responses in human white adipocytes
Live-cell imaging identifies cAMP microdomains regulating β-adrenoceptor-subtype-specific lipolytic responses in human white adipocytes Open
Lipolysis of stored triglycerides is stimulated via β-adrenergic receptor (β-AR)/3',5'-cyclic adenosine monophosphate (cAMP) signaling and inhibited via phosphodiesterases (PDEs). In type 2 diabetes, a dysregulation in the storage/lipolysi…
View article: CRISPR/Cas9 knockout in primary neonatal and adult cardiomyocytes reveals distinct cAMP dynamics regulation by various PDE2A and PDE3A isoforms
CRISPR/Cas9 knockout in primary neonatal and adult cardiomyocytes reveals distinct cAMP dynamics regulation by various PDE2A and PDE3A isoforms Open
Supplementary Figures and Tables
View article: CRISPR/Cas9 knockout in primary neonatal and adult cardiomyocytes reveals distinct cAMP dynamics regulation by various PDE2A and PDE3A isoforms
CRISPR/Cas9 knockout in primary neonatal and adult cardiomyocytes reveals distinct cAMP dynamics regulation by various PDE2A and PDE3A isoforms Open
1. Supplementary Figures and Tables 2. Plasmid sequences
View article: Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism
Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism Open
Aims Atrial fibrillation (AF) is associated with altered cAMP/PKA signaling and an AF-promoting reduction of L-type Ca2+-current (ICa,L), the mechanisms of which are poorly understood. Cyclic-nucleotide phosphodiesterases (PDEs) degrade cA…
View article: Division of labor and cooperation between different butyrophilin proteins controls phosphoantigen-mediated activation of human γδ T cells
Division of labor and cooperation between different butyrophilin proteins controls phosphoantigen-mediated activation of human γδ T cells Open
Butyrophilin (BTN)-3A and BTN2A1 molecules control TCR-mediated activation of human Vγ9Vδ2 T-cells triggered by phosphoantigens (PAg) from microbes and tumors, but the molecular rules governing antigen sensing are unknown. Here we establis…
View article: A-Kinase Anchoring Proteins in Cardiac Myocytes and Their Roles in Regulating Calcium Cycling
A-Kinase Anchoring Proteins in Cardiac Myocytes and Their Roles in Regulating Calcium Cycling Open
The rate of calcium cycling and calcium transient amplitude are critical determinants for the efficient contraction and relaxation of the heart. Calcium-handling proteins in the cardiac myocyte are altered in heart failure, and restoring t…