ArticleThe Journal of clinical investigation2025
Erythrocyte-derived extracellular vesicles induce endothelial dysfunction through arginase-1 and oxidative stress in type 2 diabetes.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of L-citrulline supplementation and watermelon intake on arterial stiffness and endothelial function in middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials.Frontiers in nutrition · 2025Pooled it
- Bioreactor-derived EVs from placental MSCs show context- and donor-specific immunomodulatory trends in human 3D lung inflammatory models.Stem cell research & therapy · 2026Article
- Association between endothelial activation and stress index and mortality in critically ill patients with diabetes mellitus: a retrospective cohort study.BMC endocrine disorders · 2026Article
- Operon™ Platform-Enabled for Cardiometabolic Biomarker Screening and Precision Treatment Strategies: A Type 2 Diabetes-Centered Review with Cardiovascular Extension.International journal of molecular sciences · 2026Review
- Hemorheological Alterations as a Driver of Microangiopathy in Diabetic Kidney Disease-The Role of Erythrocyte.International journal of molecular sciences · 2026Review
- Circular RNAs as diagnostic biomarkers in type 2 diabetes mellitus: implications in metabolic dysfunction and immune-inflammatory crosstalk.Frontiers in immunology · 2026Review
- The Association of Diabetes and Atherosclerosis: Understanding the Molecular Mechanism of the Double Burden.Current medicinal chemistry · 2026Review
- Elevated red blood cell-derived extracellular vesicles under hyperglycemic conditions are associated with CD47 expression and production of intracellular reactive oxygen species.Biomedical reports · 2025Article
- Endothelial dysfunction in patients with type 2 diabetes: the truth is in the blood.The Journal of clinical investigation · 2025Article
- Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease.Diabetes & metabolism journal · 2025Review
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Authors and funding
19 authors.
Funding
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Abstract
Red blood cells (RBCs) induce endothelial dysfunction in type 2 diabetes (T2D), but the mechanism by which RBCs communicate with the endothelium is unknown. This study tested the hypothesis that extracellular vesicles (EVs) secreted by RBCs act as mediators of endothelial dysfunction in T2D. Despite a lower production of EVs derived from RBCs of T2D patients (T2D RBC-EVs), their uptake by endothelial cells was greater than that of EVs derived from RBCs of healthy individuals (H RBC-EVs). T2D RBC-EVs impaired endothelium-dependent relaxation, and this effect was attenuated following inhibition of arginase in EVs. Inhibition of vascular arginase or oxidative stress also attenuated endothelial dysfunction induced by T2D RBC-EVs. Arginase-1 was detected in RBC-derived EVs, and arginase-1 and oxidative stress were increased in endothelial cells following coincubation with T2D RBC-EVs. T2D RBC-EVs also increased arginase-1 protein in endothelial cells following mRNA silencing and in the endothelium of aortas from endothelial cell arginase-1-knockout mice. It is concluded that T2D-RBCs induce endothelial dysfunction through increased uptake of EVs that transfer arginase-1 from RBCs to the endothelium to induce oxidative stress and endothelial dysfunction. These results shed important light on the mechanism underlying endothelial dysfunction mediated by RBCs in T2D.
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