ArticleCirculation. Heart failure2020
Phosphodiesterase 9a Inhibition in Mouse Models of Diastolic Dysfunction.
Article in Circulation. Heart failure, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Correlates of Plasma NT-proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial.Journal of the American Heart Association · 2024Trial
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).Cardiovascular research · 2025Article
- VEGFC/VEGFR3 Signaling-Dependent Lymphatic Remodeling Modulates Cardiac Response to Pressure Overload.Journal of the American Heart Association · 2025Article
- Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025Review
- PDE9A Promotes Calcium-Handling Dysfunction in Right Heart Failure via cGMP-PKG Pathway Suppression: A Mechanistic and Therapeutic Review.International journal of molecular sciences · 2025Review
- Echocardiographic Assessment of Cardiac Function in Mouse Models of Heart Disease.International journal of molecular sciences · 2025Review
- An ovary-intact postmenopausal HFpEF mouse model; menopause is more than just estrogen deficiency.American journal of physiology. Heart and circulatory physiology · 2025Article
- Cardiometabolic Phenotype in HFpEF: Insights from Murine Models.Biomedicines · 2025Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF.Microcirculation (New York, N.Y. : 1994) · 2024Article
- Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.GeroScience · 2024Article
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation.Nature cardiovascular research · 2023Article
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Inflammatory Mechanisms in Heart Failure with Preserved Ejection Fraction.Physiology (Bethesda, Md.) · 2023Review
- State-of-the-art methodologies used in preclinical studies to assess left ventricular diastolic and systolic function in mice, pitfalls and troubleshooting.Frontiers in cardiovascular medicine · 2023Review
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease.American heart journal plus : cardiology research and practice · 2022Article
- Shortening the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating sarcomere length range.Journal of molecular and cellular cardiology · 2022Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLow myocardial cGMP-PKG (cyclic guanosine monophosphate-protein kinase G) activity has been associated with increased cardiomyocyte diastolic stiffness in heart failure with preserved ejection fraction. Cyclic guanosine monophosphate is mainly hydrolyzed by PDE (phosphodiesterases) 5a and 9a. Importantly, PDE9a expression has been reported to be upregulated in human heart failure with preserved ejection fraction myocardium and chronic administration of a PDE9a inhibitor reverses preestablished cardiac hypertrophy and systolic dysfunction in mice subjected to transverse aortic constriction (TAC). We hypothesized that inhibiting PDE9a activity ameliorates diastolic dysfunction.
methodsTo examine the effect of chronic PDE9a inhibition, 2 diastolic dysfunction mouse models were studied: (1) TAC-deoxycorticosterone acetate and (2)
resultsFor acute inhibition, no cellular stiffness reduction was found, whereas chronic PDE9a inhibition resulted in reduced left ventricular chamber stiffness in TAC-deoxycorticosterone acetate, but not in
conclusionsChronic PDE9a inhibition lowers left ventricular chamber stiffness in TAC-deoxycorticosterone acetate mice. However, the usefulness of PDE9a inhibition to treat high-diastolic stiffness may be limited as the required PDE9a inhibitor dose also impairs systolic function, observed as a decline in ventricular-arterial coordination, in this model.
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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.