ArticleJCI insight2018
Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 29 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
- Incremental effects of vericiguat added to sacubitril/valsartan in heart failure with nonpreserved ejection fraction: a real-world study.International journal of cardiology. Heart & vasculature · 2026Article
- LncRNA Foxo6os as a Novel " Scaffold" Mediates MYBPC3 in Combating Pathological Cardiac Hypertrophy and Heart Failure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Myocardial fibrosis and calcification are attenuated by microRNA-129-5p targeting Asporin and Sox9 in cardiac fibroblasts.JCI insight · 2023Article
- Expression of cardiovascular-related microRNAs is altered in L-arginine:glycine amidinotransferase deficient mice.Scientific reports · 2022Article
- Cyclic GMP and PKG Signaling in Heart Failure.Frontiers in pharmacology · 2022Review
- Current Modulation of Guanylate Cyclase Pathway Activity-Mechanism and Clinical Implications.Molecules (Basel, Switzerland) · 2021Review
- treeclimbR pinpoints the data-dependent resolution of hierarchical hypotheses.Genome biology · 2021Article
- The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction.Signal transduction and targeted therapy · 2021Article
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
- CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload-Induced Heart Failure.Circulation. Heart failure · 2021Article
- PERK-Mediated Suppression of microRNAs by Sildenafil Improves Mitochondrial Dysfunction in Heart Failure.iScience · 2020Article
- PDE5 inhibitor sildenafil attenuates cardiac microRNA 214 upregulation and pro-apoptotic signaling after chronic alcohol ingestion in mice.Molecular and cellular biochemistry · 2020Article
- Phosphodiesterase 9a Inhibition in Mouse Models of Diastolic Dysfunction.Circulation. Heart failure · 2020Article
- Phosphorylation Modifications Regulating Cardiac Protein Quality Control Mechanisms.Frontiers in physiology · 2020Review
- Targeting Protein Kinase G to Treat Cardiac Proteotoxicity.Frontiers in physiology · 2020Review
- Leveraging Signaling Pathways to Treat Heart Failure With Reduced Ejection Fraction.Circulation research · 2019Review
- YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis In Vivo.Developmental cell · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
MicroRNAs (miRs) posttranscriptionally regulate mRNA and its translation into protein, and are considered master controllers of genes modulating normal physiology and disease. There is growing interest in how miRs change with drug treatment, and leveraging this for precision guided therapy. Here we contrast 2 closely related therapies, inhibitors of phosphodiesterase type 5 or type 9 (PDE5-I, PDE9-I), given to mice subjected to sustained cardiac pressure overload (PO). Both inhibitors augment cyclic guanosine monophosphate (cGMP) to activate protein kinase G, with PDE5-I regulating nitric oxide (NO) and PDE9-I natriuretic peptide-dependent signaling. While both produced strong phenotypic improvement of PO pathobiology, they surprisingly showed binary differences in miR profiles; PDE5-I broadly reduces more than 120 miRs, including nearly half those increased by PO, whereas PDE9-I has minimal impact on any miR (P < 0.0001). The disparity evolves after pre-miR processing and is organ specific. Lastly, even enhancing NO-coupled cGMP by different methods leads to altered miR regulation. Thus, seemingly similar therapeutic interventions can be barcoded by profound differences in miR signatures, and reversing disease-associated miR changes is not required for therapy success.
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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.