ArticleJournal of the American Heart Association2021
Serum-Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Adipose-Derived Extracellular Vesicles and Intercellular Crosstalk With Skeletal Muscle: Implications for Sarcopenic Obesity and Metabolic Dysregulation.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Muscle-specific miR-499-5p delivered by small extracellular vesicles impairs endothelial function and ischemic hindlimb recovery in diabetic mice.Cardiovascular diabetology · 2025Article
- Podoplanin-positive cell-derived small extracellular vesicles contribute to cardiac amyloidosis after myocardial infarction.Cell reports · 2025Article
- Exosomal RNAs and EZH2: unraveling the molecular dialogue driving tumor progression.Medical oncology (Northwood, London, England) · 2025Review
- Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure.Circulation research · 2024Article
- Systematic review and bioinformatics analysis of plasma and serum extracellular vesicles proteome in type 2 diabetes.Heliyon · 2024Article
- Research advances in the therapy of metabolic syndrome.Frontiers in pharmacology · 2024Review
- Immunometabolism, extracellular vesicles and cardiac injury.Frontiers in endocrinology · 2023Review
- Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Diabetes impairs cardioprotective function of endothelial progenitor cell-derived extracellular vesicles via H3K9Ac inhibition.Theranostics · 2022Article
- Serum-Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2.Journal of the American Heart Association · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Background Impaired angiogenic abilities of the microvascular endothelial cell (MVEC) play a crucial role in diabetes mellitus-impaired ischemic tissue repair. However, the underlying mechanisms of diabetes mellitus-impaired MVEC function remain unclear. We studied the role of serum-derived small extracellular vesicles (ssEVs) in diabetes mellitus-impaired MVEC function. Methods and Results ssEVs were isolated from 8-week-old male db/db and db/+ mice by ultracentrifugation and size/number were determined by the Nano-sight tracking system. Diabetic ssEVs significantly impaired tube formation and migration abilities of human MVECs. Furthermore, local transplantation of diabetic ssEVs strikingly reduced blood perfusion and capillary/arteriole density in ischemic hind limb of wildtype C57BL/6J mice. Diabetic ssEVs decreased secretion/expression of several pro-angiogenic factors in human MVECs. Mechanistically, expression of enhancer of zest homolog 2 (EZH2), the major methyltransferase responsible for catalyzing H3K27me3 (a transcription repressive maker), and H3K27me3 was increased in MVECs from db/db mice. Diabetic ssEVs increased EZH2 and H3K27me3 expression/activity in human MVECs. Expression of EZH2 mRNA was increased in diabetic ssEVs. EZH2-specific inhibitor significantly reversed diabetic ssEVs-enhanced expression of EZH2 and H3K27me3, impaired expression of angiogenic factors, and improved blood perfusion and vessel density in ischemic hind limb of C57BL/6J mice. Finally, EZH2 inactivation repressed diabetic ssEVs-induced H3K27me3 expression at promoter of pro-angiogenic genes. Conclusions Diabetic ssEVs impair the angiogenic property of MVECs via, at least partially, transferring EZH2 mRNA to MVECs, thus inducing the epigenetic mechanism involving EZH2-enhanced expression of H3K27me3 and consequent silencing of pro-angiogenic genes. Our findings unravel the cellular mechanism and expand the scope of bloodborne substances that impair MVEC function in diabetes mellitus.
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