ArticleNature2014
Inhibition of miR-25 improves cardiac contractility in the failing heart.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
224 citing papers in PubMed, 1 synthesis or guideline pooled it, 407 citations in OpenAlex.
- The microRNA Expression Profiling in Heart Failure: A Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Associations of osteopontin and NT-proBNP with circulating miRNA levels in acute coronary syndrome.Physiological genomics · 2019Trial
- PlanHab (Planetary Habitat Simulation): the combined and separate effects of 21 days bed rest and hypoxic confinement on human skeletal muscle miRNA expression.Physiological reports · 2016Trial
- Pathological Mechanisms and Therapeutic Potential of Mitochondrial Dysfunction in Heart Failure.Reviews in cardiovascular medicine · 2026Review
- Article
- Circulating microRNAs in Atrial Fibrillation: Clinical Significance and Future Perspectives.Medicina (Kaunas, Lithuania) · 2026Review
- Plasma Micro-RNA Signatures of Type 1 Ryanodine Receptor Related Myopathies.bioRxiv : the preprint server for biology · 2026Article
- Emerging roles of microRNAs and other non-coding transcriptome in muscular dystrophies.Inflammation and regeneration · 2026Review
- The Landscape of SERCA2 in Cardiovascular Diseases: Expression Regulation, Therapeutic Applications, and Emerging Roles.Biomolecules · 2026Review
- Bridging miRNA Research with Clinical Applications in Cardiovascular Diseases: Advances in Delivery Systems and Therapeutic Strategies.Mini reviews in medicinal chemistry · 2026Review
- RNA Therapeutics in Heart Failure.Journal of cardiovascular translational research · 2025Review
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- New Frontiers of microRNA in Heart Failure: From Clinical Risk to Therapeutic Applications.Journal of clinical medicine · 2025Review
- miR-140-5p and Water Channel Aquaporin 4: Opening a New Channel for Treating Atrial Fibrillation.Korean circulation journal · 2025Article
- 17(R)-Resolvin D1 protects against sickle cell-related inflammatory cardiomyopathy in humanized mice.Blood · 2025Article
- Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications.International journal of molecular sciences · 2025Review
- MiR-25-3p regulates pulmonary arteriovenous malformation after Glenn procedure in patients with univentricular heart via the PHLPP2-HIF-1α axis.Scientific reports · 2025Article
- Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia-Reperfusion Injury Model.Antioxidants (Basel, Switzerland) · 2025Article
- MicroRNA: unveiling novel mechanistic and theranostic pathways in diabetic cardiomyopathy.Frontiers in pharmacology · 2025Review
- Profiling Reduced Expression of Contractile and Mitochondrial mRNAs in the Human Sinoatrial Node vs. Right Atrium and Predicting Their Suppressed Expression by Transcription Factors and/or microRNAs.International journal of molecular sciences · 2024Article
164 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Heart failure is characterized by a debilitating decline in cardiac function, and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy. MicroRNAs (miRNAs) are dysregulated in heart failure but whether they control contractility or constitute therapeutic targets remains speculative. Using high-throughput functional screening of the human microRNAome, here we identify miRNAs that suppress intracellular calcium handling in heart muscle by interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 markedly halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR oligonucleotide. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggest that it might be targeted therapeutically to restore function.
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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.