Diabetes affects extracellular vesicle content and function

Introduction: The role of circulating extracellular vesicles in cardiovascular diseases remains incompletely understood.We previously demonstrated that extracellular vesicles circulating in plasma of healthy mice can suppress monocyte activation through transfer of anti-inflammatory microRNAs. Here we set out to determine the effect of diabetes on the function of plasma extracellular vesicles since diabetes is known to negatively affect vascular function, playing a contributory role in cardiovascular diseases. Methods: Circulating plasma extracellular vesicles were isolated from mouse and rat models of type 2 diabetes. Extracellular vesicles were
characterised with nanoparticle tracking analysis. Furthermore, qPCR and RNA-sequencing approaches were used to characterise vesicle content and function. Results: We found that vesicle abundance and size were increased in mouse and rat models of type 2 diabetes. MicroRNAs in plasma extracellular vesicles were dysregulated during the progression of diabetes in thesemodels. Finally, we demonstrate that vesicles isolated from diabetic plasma can activate inflammatory pathways in endothelial cells. Current studies are seeking to determine the contribution of microRNA transfer to endothelial dysfunction. Conclusions: These studies suggest that the microRNA content and function of extracellular vesicles are dysregulated during diabetes.
Advancements in this area could facilitate the development of more effective non-invasive diagnostics, prognostics, and therapeutics. Funding: Supported by funding from the Canadian Vascular Network and the Canadian Institutes of Health Research.