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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2020

Open Access 01-12-2020 | Diabetes | Research

Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration

Authors: Sharon F. Wu, Nicole Noren Hooten, David W. Freeman, Nicolle A. Mode, Alan B. Zonderman, Michele K. Evans

Published in: Journal of Translational Medicine | Issue 1/2020

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Abstract

Background

Inflammation-related atherosclerotic peripheral vascular disease is a major end organ complication of diabetes mellitus that results in devastating morbidity and mortality. Extracellular vesicles (EVs) are nano-sized particles that contain molecular cargo and circulate in the blood. Here, we examined EV protein cargo from diabetic individuals and whether these EVs cause functional changes in endothelial cells.

Methods

We quantified inflammatory protein levels in plasma-derived EVs from a longitudinal cohort of euglycemic and diabetic individuals and used in vitro endothelial cell biological assays to assess the functional effects of these EVs with samples from a cross-sectional cohort.

Results

We found several significant associations between EV inflammatory protein levels and diabetes status. The angiogenic factor, vascular endothelial growth factor A (VEGF-A), was associated with diabetes status in our longitudinal cohort. Those with diabetes mellitus had higher EV VEGF-A levels compared to euglycemic individuals. Additionally, EV levels of VEGF-A were significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). To test whether EVs with different inflammatory cargo can demonstrate different effects on endothelial cells, we performed cell migration and immunofluorescence assays. We observed that EVs from diabetic individuals increased cell lamellipodia formation and migration when compared to EVs from euglycemic individuals.

Conclusions

Higher levels of inflammatory proteins were found in EVs from diabetic individuals. Our data implicate EVs as playing important roles in peripheral vascular disease that occur in individuals with diabetes mellitus and suggest that EVs may serve as an informative diagnostic tool for the disease.
Appendix
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Metadata
Title
Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration
Authors
Sharon F. Wu
Nicole Noren Hooten
David W. Freeman
Nicolle A. Mode
Alan B. Zonderman
Michele K. Evans
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Diabetes
Published in
Journal of Translational Medicine / Issue 1/2020
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-020-02398-6

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