ArticleJournal of molecular and cellular cardiology2015
A critical role of cardiac fibroblast-derived exosomes in activating renin angiotensin system in cardiomyocytes.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 3 of them syntheses that pooled it.
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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
127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Differences in the cargos and functions of exosomes derived from six cardiac cell types: a systematic review.Stem cell research & therapy · 2019Pooled it
- Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology.Cardiovascular research · 2018Guideline
- Angiotensinogen M235T polymorphism and susceptibility to hypertrophic cardiomyopathy in Asian population: A meta analysis.Journal of the renin-angiotensin-aldosterone system : JRAASPooled it
- Pharmacological Inhibition of Small Extracellular Vesicle Secretion by ALK5i SD-208 via Lysosomal Rerouting of CD63+ Compartments.Journal of extracellular vesicles · 2026Article
- Extracellular Vesicles in Cardiovascular Disease: Intercellular Signaling, Liquid Biopsy Biomarkers, and Therapeutic Translation.Circulation research · 2026Review
- Extracellular Vesicles in Cardiac Cell Crosstalk: from Intercellular Communication to Clinical Translation.Cardiovascular drugs and therapy · 2026Review
- Extracellular vesicles in the heart: mediators of intercellular communication in health and disease in vitro.Cell communication and signaling : CCS · 2026Review
- Comparative analysis of extracellular vesicles released from resting neutrophils under distinct pharmacological inhibition.Scientific reports · 2026Article
- Exosomes Regulate the NLRP3/Caspase-1/IL-1β Signaling Pathway in Parkinson's Disease: Mechanisms of Neuroinflammation Modulation and α-Synuclein Propagation.Neuropsychiatric disease and treatment · 2026Review
- Potential Biomarker and Therapeutic Tools for Pathological Cardiac Hypertrophy and Heart Failure: Extracellular Vesicles.International journal of molecular sciences · 2025Review
- Cardiac Myofibroblast-Derived Small Extracellular Vesicles Moderate Fibrotic Responses via piRNA-62788/PIWIL2-Mediated SRF Silencing.Journal of extracellular vesicles · 2025Article
- Revisiting renin-angiotensin-aldosterone system in aging: translational insights from bench to bedside and back.The Journal of clinical investigation · 2025Review
- Atrial Fibroblasts-Derived Extracellular Vesicles Exacerbate Atrial Arrhythmogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Recent advances in the roles of extracellular vesicles in cardiovascular diseases: pathophysiological mechanisms, biomarkers, and cell-free therapeutic strategy.Molecular medicine (Cambridge, Mass.) · 2025Review
- Review
- Exploring the landscape of exosomes in heart failure: a bibliometric analysis.International journal of surgery (London, England) · 2025Review
- Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity.International journal of molecular sciences · 2025Article
- Competitive signaling and cellular communications in myocardial infarction response.Molecular biology reports · 2025Review
- Adipose-derived exosomes ameliorate skeletal muscle atrophy via miR-146a-5p/IGF-1R signaling.Journal of nanobiotechnology · 2024Article
- Exosome-based therapies for inflammatory disorders: a review of recent advances.Stem cell research & therapy · 2024Review
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. However, the precise underlying mechanisms have not been fully delineated. Herein we report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy. In cultured CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT1R) and 2 (AT2R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFβ)1 or hydrogen peroxide did not. The CF-derived exosomes upregulated the expression of renin, angiotensinogen, AT1R, and AT2R, downregulated angiotensin-converting enzyme 2, and enhanced Ang II production in cultured cardiomyocytes. In addition, the CF exosome-induced cardiomyocyte hypertrophy was blocked by both AT1R and AT2R antagonists. Exosome inhibitors, GW4869 and dimethyl amiloride (DMA), inhibited CF-induced cardiomyocyte hypertrophy with little effect on Ang II-induced cardiomyocyte hypertrophy. Mechanistically, CF exosomes upregulated RAS in cardiomyocytes via the activation of mitogen-activated protein kinases (MAPKs) and Akt. Finally, Ang II-induced exosome release from cardiac fibroblasts and pathological cardiac hypertrophy were dramatically inhibited by GW4869 and DMA in mice. These findings demonstrate that Ang II stimulates CFs to release exosomes, which in turn increase Ang II production and its receptor expression in cardiomyocytes, thereby intensifying Ang II-induced pathological cardiac hypertrophy. Accordingly, specific targeting of Ang II-induced exosome release from CFs may serve as a novel therapeutic approach to treat cardiac pathological hypertrophy and heart failure.
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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.