ArticlePloS one2015
The emperor's new clothes: PDE5 and the heart.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Alterations in cardiac contractile and regulatory proteins contribute to age-related cardiac dysfunction in male rats.Physiological reports · 2024Article
- Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.Frontiers in endocrinology · 2024Review
- Aging related decreases in NM myosin expression and contractility in a resistance vessel.Frontiers in physiology · 2024Article
- Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension: Focus on Phosphodiesterase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 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
- Phosphodiesterase 9a Inhibition in Mouse Models of Diastolic Dysfunction.Circulation. Heart failure · 2020Article
- The vasculature in HFpEF vs HFrEF: differences in contractile protein expression produce distinct phenotypes.Heliyon · 2020Article
- Enhanced Cardiomyocyte Function in Hypertensive Rats With Diastolic Dysfunction and Human Heart Failure Patients After Acute Treatment With Soluble Guanylyl Cyclase (sGC) Activator.Frontiers in physiology · 2020Article
- Posttranslational modifications of titin from cardiac muscle: how, where, and what for?The FEBS journal · 2019Review
- 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
- Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap.Circulation · 2016Review
- Chemotherapeutic efficacy of phosphodiesterase inhibitors in chagasic cardiomyopathy.JACC. Basic to translational science · 2016Article
- Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy.Inflammation · 2016Article
- Phosphodiesterase type 5 inhibitors: back and forward from cardiac indications.Journal of endocrinological investigation · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Phosphodiesterase-5 (PDE5) is highly expressed in the pulmonary vasculature, but its expression in the myocardium is controversial. Cyclic guanosine monophosphate (cGMP) activates protein kinase G (PKG), which has been hypothesized to blunt cardiac hypertrophy and negative remodeling in heart failure. Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) failed to show a beneficial effect. These results highlight the controversy regarding the role and expression of PDE5 in the healthy and failing heart. This study used one- and two-dimensional electrophoresis and Western blotting to examine PDE5 expression in mouse (before and after trans-aortic constriction), dog (control and HFpEF) as well as human (healthy and failing) heart. We were unable to detect PDE5 in any cardiac tissue lysate, whereas PDE5 was present in the murine and bovine lung samples used as positive controls. These results indicate that if PDE5 is expressed in cardiac tissue, it is present in very low quantities, as PDE5 was not detected in either humans or any model of heart failure examined. Therefore in cardiac muscle, it is unlikely that PDE5 is involved the regulation of cGMP-PKG signaling, and hence PDE5 does not represent a suitable drug target for the treatment of cardiac hypertrophy. These results highlight the importance of rigorous investigation prior to clinical trial design.
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What OpenQuestion holds
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.