ArticleProceedings of the National Academy of Sciences of the United States of America2016
PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
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- Integrated Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulations Accelerate the Discovery of Novel PDE1 Inhibitors with Potential for the Treatment of Idiopathic Pulmonary Fibrosis.Molecules (Basel, Switzerland) · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Genome-wide association analysis of composite sleep health scores in 413,904 individuals.Communications biology · 2025Article
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- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Antibody-assisted selective isolation of Purkinje cell nuclei from mouse cerebellar tissue.Cell reports methods · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
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- The H2Bub1-deposition complex is required for human and mouse cardiogenesis.Development (Cambridge, England) · 2023Article
- Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental?Circulation research · 2023Article
- Characterization of a robust mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2023Article
- PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth.Circulation research · 2023Article
- An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.Circulation research · 2023Article
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
- Association of Cardiovascular Health Through Young Adulthood With Genome-Wide DNA Methylation Patterns in Midlife: The CARDIA Study.Circulation · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
Abstract
Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β-stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance.
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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.