ArticleProceedings of the National Academy of Sciences of the United States of America2015
Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
- PDE3B as a multi-organ therapeutic node in the gut-liver axis of metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2026Article
- MG53, a Regenerative Myokine Linking Skeletal Muscle to Cardiac Repair.Biomolecules · 2026Review
- Gait analysis for functional evaluation in a surgical hindlimb suspension model of muscle atrophy.The Journal of physiology · 2026Article
- Separating the genetics of disease, treatment, and treatment response using graphical modeling and large-scale electronic health records.medRxiv : the preprint server for health sciences · 2026Article
- Genome-wide analysis of cardiac ventricular phenotypes reveals novel loci and therapeutic targets for heart failure.Nature communications · 2026Article
- Covalent Binding of the Boronic Acid-Based Inhibitor GSK4394835A to Phosphodiesterase 3B, a Drug Target for Cardiovascular Disease.Journal of medicinal chemistry · 2025Article
- Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling.Current heart failure reports · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism.Physiological reports · 2024Article
- Identification of a mechanism promoting mitochondrial sterol accumulation during myocardial ischemia-reperfusion: role of TSPO and STAR.Basic research in cardiology · 2024Article
- Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection.Nature communications · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Advances in the Study of MG53 in Cardiovascular Disease.International journal of general medicine · 2023Review
- MG53 preserves mitochondrial integrity of cardiomyocytes during ischemia reperfusion-induced oxidative stress.Redox biology · 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
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
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Authors and funding
19 authors at 9 institutions in 4 countries.
Funding
Abstract
Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B(-/-) heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling. Compared with WT mitochondria, PDE3B(-/-) mitochondria were enriched in antiapoptotic Bcl-2, produced less reactive oxygen species, and more frequently contacted transverse tubules where PDE3B was localized with caveolin-3. Moreover, a PDE3B(-/-) mitochondrial fraction containing connexin-43 and caveolin-3 was more resistant to Ca(2+)-induced opening of the mitochondrial permeability transition pore. Proteomics analyses indicated that PDE3B(-/-) heart mitochondria fractions were enriched in buoyant ischemia-induced caveolin-3-enriched fractions (ICEFs) containing cardioprotective proteins. Accumulation of proteins into ICEFs was PKA dependent and was achieved by ischemic preconditioning or treatment of WT heart with the PDE3 inhibitor cilostamide. Taken together, these findings indicate that PDE3B deletion confers cardioprotective effects because of cAMP/PKA-induced preconditioning, which is associated with the accumulation of proteins with cardioprotective function in ICEFs. To our knowledge, our study is the first to define a role for PDE3B in cardioprotection against I/R injury and suggests PDE3B as a target for cardiovascular therapies.
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