ArticleThe Journal of clinical investigation2019
microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 6 of them syntheses that pooled it.
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
203 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Harnessing exosomes in dry eye disease: a triple threat approach.BMC ophthalmology · 2026Pooled it
- Diagnostic and prognostic value of circulating microRNA-21 in heart failure: A systematic review and meta-analysis.Biomolecules & biomedicine · 2025Pooled it
- Therapeutic Potential of Exosome for Cardiac Arrhythmia: A Systematic Review of Preclinical Evidence.Stem cell reviews and reports · 2025Pooled it
- Extracellular Vesicles as a Cell-free Therapy for Cardiac Repair: a Systematic Review and Meta-analysis of Randomized Controlled Preclinical Trials in Animal Myocardial Infarction Models.Stem cell reviews and reports · 2022Pooled it
- Progress in research on the role of exosomal miRNAs in the diagnosis and treatment of cardiovascular diseases.Frontiers in genetics · 2022Pooled it
- Meta-Analysis of the Potential Role of miRNA-21 in Cardiovascular System Function Monitoring.BioMed research international · 2020Pooled it
- Plasma Small Extracellular Vesicle Cardiac miRNA Expression in Patients with Ischemic Heart Failure, Randomized to Percutaneous Intramyocardial Treatment of Adipose Derived Stem Cells or Placebo: Subanalysis of the SCIENCE Study.International journal of molecular sciences · 2023Trial
- Review
- Small Extracellular Vesicles in Cardioprotection, Cardiac Repair, and Regeneration: Cargo Mechanisms, Producer Cell Sources, and Translational Development.Biomedicines · 2026Review
- Biomaterial-Assisted Stem Cell Therapy and Exosome Delivery in Myocardial Infarction: A Narrative Review.Biomimetics (Basel, Switzerland) · 2026Review
- MiR-21-5p Protects Embryonic Growth and Heart Function During Developmental Hypoxia by Dampening HIF Responses and Altering Gene Expression.Comprehensive Physiology · 2026Article
- Synthetically designed circRNA can be used to target cardiovascular relevant microRNAs to improve cellular function.Scientific reports · 2026Article
- The dual face of human chorionic gonadotropin in the CNS: neuroprotection, signaling, and possible pathological effects.Archives of gynecology and obstetrics · 2026Review
- Review
- Dynamic microRNA Signatures as Biomarkers for Cardiac Ischemia and Remodeling.International journal of molecular sciences · 2026Article
- Bioengineered Cellular and Acellular Therapies for Ischemic Heart Disease in Clinically Relevant Models.Bioengineering (Basel, Switzerland) · 2026Review
- Extracellular vesicles in heart failure: bridging pathogenic insights, diagnostic utility, and therapeutic applications.Frontiers in pharmacology · 2026Review
- The Dual Role of Extracellular Vesicles in Aging and Age-Related Diseases: Pathophysiology and Therapeutic Potential.International journal of nanomedicine · 2026Review
- Harnessing Natural Extracellular Vesicles to Combat Age-Related Diseases: From Aging Drivers to Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- Heterogeneity and Clinical Translation of Cardiac-Derived Extracellular Vesicles in Heart Failure: From Mechanisms to Precision Therapeutics.Reviews in cardiovascular medicine · 2026Review
143 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Exosomes, as functional paracrine units of therapeutic cells, can partially reproduce the reparative properties of their parental cells. The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. We isolated exosomes from explant-derived cardiac stromal cells from patients with heart failure (FEXO) or from normal donor hearts (NEXO) and compared their regenerative activities in vitro and in vivo. Patients in the FEXO group exhibited an impaired ability to promote endothelial tube formation and cardiomyocyte proliferation in vitro. Intramyocardial injection of NEXO resulted in structural and functional improvements in a murine model of acute myocardial infarction. In contrast, FEXO therapy exacerbated cardiac function and left ventricular remodeling. microRNA array and PCR analysis revealed dysregulation of miR-21-5p in FEXO. Restoring miR-21-5p expression rescued FEXO's reparative function, whereas blunting miR-21-5p expression in NEXO diminished its therapeutic benefits. Further mechanistic studies revealed that miR-21-5p augmented Akt kinase activity through the inhibition of phosphatase and tensin homolog. Taken together, the heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway.
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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.