ArticleCirculation. Heart failure2012
Differential expression of PDE5 in failing and nonfailing human myocardium.
Article in Circulation. Heart failure, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Trial
- PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial: rationale and design.Circulation. Heart failure · 2012Trial
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.Frontiers in endocrinology · 2024Review
- Sildenafil affects the human Kir2.1 and Kir2.2 channels at clinically relevant concentrations: Inhibition potentiated by low BaFrontiers in pharmacology · 2023Article
- Phosphodiesterase 5a Signalling in Skeletal Muscle Pathophysiology.International journal of molecular sciences · 2022Article
- Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension: Focus on Phosphodiesterase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Cyclic GMP and PKG Signaling in Heart Failure.Frontiers in pharmacology · 2022Review
- Myocardial Impact of NHE1 Regulation by Sildenafil.Frontiers in cardiovascular medicine · 2021Review
- Type 5 phosphodiesterase (PDE5) and the vascular tree: From embryogenesis to aging and disease.Mechanisms of ageing and development · 2020Review
- Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence.Nature reviews. Cardiology · 2020Review
- Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.Cardiovascular drugs and therapy · 2020Review
- cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway.Basic research in cardiology · 2018Review
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells.Stem cells (Dayton, Ohio) · 2017Article
- Inhalative and intravenous stimulation of soluble guanylate cyclase reduces pulmonary vascular resistance and increases cardiac output in experimental septic shock.Experimental and therapeutic medicine · 2017Article
- Cardiac Phosphodiesterases and Their Modulation for Treating Heart Disease.Handbook of experimental pharmacology · 2017Review
- Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G.Cardiovascular research · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRecognizing that inhibitors of phosphodiesterase type 5 (PDE5) are increasingly employed in patients with pulmonary hypertension and right ventricular (RV) failure, we examined PDE5 expression in the human RV and its impact on myocardial contractility. METHODS AND
resultsTissue extracts from the RV of 20 patients were assayed for PDE5 expression using immunoblot and immunohistochemical staining. Tissues were selected from groups of nonfailing organ donors and transplant recipients with endstage ischemic cardiomyopathy or idiopathic dilated cardiomyopathy. Among dilated cardiomyopathy patients, subgroups with mild or severe RV dysfunction and prior left ventricular assist devices were analyzed separately. Our results showed that PDE5 abundance increased more than 4-fold in the RVs of the ischemic cardiomyopathy compared with the nonfailing group. In dilated cardiomyopathy, PDE5 upregulation was more moderate and varied with the severity of RV dysfunction. Immunohistochemical staining confirmed that cardiac myocytes contributed to the upregulation in the failing hearts. In functional studies, PDE5 inhibition produced little change in developed force in RV trabeculae from nonfailing hearts but produced a moderate increase in RV trabeculae from failing hearts.
conclusionsOur results showed the etiology- and severity-dependent upregulation of myocyte PDE5 expression in the RV and the impact of this upregulation on myocardial contractility. These findings suggest that RV PDE5 expression could contribute to the pathogenesis of RV failure, and direct myocardial responses to PDE5 inhibition may modulate the indirect responses mediated by RV afterload reduction.
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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.