ArticleScientific reports2017
Hepatocyte-secreted extracellular vesicles modify blood metabolome and endothelial function by an arginase-dependent mechanism.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 86 citations in OpenAlex.
- Exploring differences in protein cargo of extracellular vesicles from ME/CFS patient plasma compared to healthy controls.Biochemistry and biophysics reports · 2026Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Tissue-Specific Extracellular Vesicles Enriched From Circulation: Exploring the Liquid Biopsy Perspective.Journal of extracellular biology · 2026Review
- Extracellular vesicles in cardiovascular homeostasis and disease: potential role in diagnosis and therapy.Nature reviews. Cardiology · 2025Review
- Chronic hypoxia induces liver injury via PKCδ/ASMase-driven ceramide accumulation and endoplasmic reticulum stress in rats.Lipids in health and disease · 2025Article
- Review
- Exosome-mediated Transfer of lncRNA in Liver Associated Diseases; Uncovered Truths.Cell biochemistry and biophysics · 2025Review
- Circulating Extracellular Vesicles in Alcoholic Liver Disease Affect Skeletal Muscle Homeostasis and Differentiation.Journal of cachexia, sarcopenia and muscle · 2025Article
- Metabolic Profiling of Brain Tissue and Brain-Derived Extracellular Vesicles in Alzheimer's Disease.Journal of extracellular vesicles · 2025Article
- Role of Redox Homeostasis in the Communication Between Brain and Liver Through Extracellular Vesicles.Antioxidants (Basel, Switzerland) · 2024Review
- Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma.Cancers · 2024Review
- Adipose mesenchymal stem cells-derived extracellular vesicles exert their preferential action in damaged central sites of SOD1 mice rather than peripherally.European journal of histochemistry : EJH · 2024Article
- Extracellular Vesicles in Lung Cancer: Implementation in Diagnosis and Therapeutic Perspectives.Cancers · 2024Review
- Article
- Metabolic features of tumor-derived extracellular vesicles: challenges and opportunities.Extracellular vesicles and circulating nucleic acids · 2024Review
- Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors.Journal of clinical and translational hepatology · 2023Review
- Seminar: Extracellular Vesicles as Mediators of Environmental Stress in Human Disease.Environmental health perspectives · 2023Article
- Role of Extracellular Vesicles in Liver Diseases.Life (Basel, Switzerland) · 2023Review
- An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism.International journal of molecular sciences · 2023Review
- A High-Throughput Colorimetric Microplate Assay for Determination of Plasma Arginase Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocytes release extracellular vesicles (EVs) loaded with signaling molecules and enzymes into the bloodstream. Although the importance of EVs in the intercellular communication is already recognized, the metabolic impact of the enzymes carried by these vesicles is still unclear. We evaluated the global effect of the enzymatic activities of EVs by performing untargeted metabolomic profiling of serum samples after their exposure to EVs. This approach revealed a significant change in the abundance of 94 serum metabolic signals. Our study shows that these vesicles modify the concentration of metabolites of different chemical nature including metabolites related to arginine metabolism, which regulates vascular function. To assess the functional relevance of this finding, we examined the levels of arginase-1 protein and its activity in the hepatic EVs carrying the exosomal markers CD81 and CD63. Remarkably, the arginase activity was also detected in EVs isolated from the serum in vivo, and this vesicular activity significantly increased under liver-damaging conditions. Finally, we demonstrated that EVs secreted by hepatocytes inhibited the acetylcholine-induced relaxation in isolated pulmonary arteries, via an arginase-dependent mechanism. In summary, our study demonstrates that the hepatocyte-released EVs are metabolically active, affecting a number of serum metabolites involved in oxidative stress metabolism and the endothelial function.
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