ArticleBasic research in cardiology2011
Conserved expression and functions of PDE4 in rodent and human heart.
Article in Basic research in cardiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed.
- Development of a Nanoscale Protein-Protein Mapping of PDE4 Interface-Disrupting Peptides.Nano letters · 2026Article
- The cAMP-phosphodiesterase PDE4B2 controls peroxisome proliferator-activated receptor γ expression and the initiation of adipogenesis in 3T3-L1 cells.American journal of physiology. Endocrinology and metabolism · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.British journal of pharmacology · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Review
- Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.Clinical and experimental rheumatology · 2025Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- PDE4D mediates impaired β-adrenergic receptor signalling in the sinoatrial node in mice with hypertensive heart disease.Cardiovascular research · 2023Article
- Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2.Circulation research · 2023Article
- Whole-heart multiparametric optical imaging reveals sex-dependent heterogeneity in cAMP signaling and repolarization kinetics.Science advances · 2023Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.Journal of molecular and cellular cardiology · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Compartmentalized cAMP signaling in cardiac ventricular myocytes.Cellular signalling · 2022Review
- Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules.Frontiers in pharmacology · 2022Review
- Micro-2D Cell Culture for cAMP Measurements Using FRET Reporters in Human iPSC-Derived Cardiomyocytes.Methods in molecular biology (Clifton, N.J.) · 2022Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
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Abstract
PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation-contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non-PDE4 activity in human hearts compared to rodents. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. Our findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has 'global' effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans. These differences may explain the distinct pharmacological effects of PDE4 inhibition in rodent and human hearts.
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