ArticleJCI insight2018
Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Bayliss Starling Prize Lecture 2023: Neuropeptide-Y being 'unsympathetic' to the broken hearted.The Journal of physiology · 2025Article
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Cardiac Sympathetic Innervation and Ventricular Arrhythmias in Structural Heart Disease: Current Peripheral Neuromodulation Therapies and Emerging Therapeutic Targets.Arrhythmia & electrophysiology review · 2025Review
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- A multiscale predictive digital twin for neurocardiac modulation.The Journal of physiology · 2023Article
- A Comparative Review of Vagal Nerve Stimulation Versus Baroreceptor Activation Therapy in Cardiac Diseases.Cureus · 2023Review
- Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Article
- C-type natriuretic peptide is a pivotal regulator of metabolic homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Dynamics of adrenergic signaling in cardiac myocytes and implications for pharmacological treatment.Journal of theoretical biology · 2021Article
- Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches.The Journal of physiology · 2020Review
- The autonomic nervous system and cardiac arrhythmias: current concepts and emerging therapies.Nature reviews. Cardiology · 2019Review
- FRET-based cyclic GMP biosensors measure low cGMP concentrations in cardiomyocytes and neurons.Communications biology · 2019Article
- Sex differences in sympathetic gene expression and cardiac neurochemistry in Wistar Kyoto rats.PloS one · 2019Article
- Calming the Nervous Heart: Autonomic Therapies in Heart Failure.Cardiac failure review · 2018Review
- Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Low-Concentration Oxygen/Ozone Treatment Attenuated Radiculitis and Mechanical Allodynia via PDE2A-cAMP/cGMP-NF-Pain research & management · 2018Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Elevated levels of brain natriuretic peptide (BNP) are regarded as an early compensatory response to cardiac myocyte hypertrophy, although exogenously administered BNP shows poor clinical efficacy in heart failure and hypertension. We tested whether phosphodiesterase 2A (PDE2A), which regulates the action of BNP-activated cyclic guanosine monophosphate (cGMP), was directly involved in modulating Ca2+ handling from stellate ganglia (SG) neurons and cardiac norepinephrine (NE) release in rats and humans with an enhanced sympathetic phenotype. SG were also isolated from patients with sympathetic hyperactivity and healthy donor patients. PDE2A activity of the SG was greater in both spontaneously hypertensive rats (SHRs) and patients compared with their respective controls, whereas PDE2A mRNA was only high in SHR SG. BNP significantly reduced the magnitude of the calcium transients and ICaN in normal Wistar Kyoto (WKY) SG neurons, but not in the SHRs. cGMP levels stimulated by BNP were also attenuated in SHR SG neurons. Overexpression of PDE2A in WKY neurons recapitulated the calcium phenotype seen in SHR neurons. Functionally, BNP significantly reduced [3H]-NE release in the WKY rats, but not in the SHRs. Blockade of overexpressed PDE2A with Bay 60-7550 or overexpression of catalytically inactive PDE2A reestablished the modulatory action of BNP in SHR SG neurons. This suggests that PDE2A may be a key target in modulating the action of BNP to reduce sympathetic hyperactivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.