Circulating small extracellular vesicles mediate vascular hyperpermeability in diabetes.

Area of Science:

• Vascular biology
• Diabetes complications
• Extracellular vesicles

Background:

• Type 2 diabetes mellitus is linked to vascular hyperpermeability and cognitive impairment.
• Cerebrovascular endothelial dysfunction is a key feature of diabetic complications.

Purpose of the Study:

• To test if circulating small extracellular vesicles (sEVs) change in type 2 diabetes to disrupt the vascular barrier.
• To investigate the role of sEVs in diabetic cerebrovascular dysfunction and cognitive decline.

Main Methods:

• Isolated sEVs from diabetic and non-diabetic mice and humans.
• Assessed sEVs' ability to disrupt endothelial cell barriers.
• Analyzed sEV contents and effects on recipient cells using proteomics and pathway inhibitors.

Main Results:

• Diabetic mice showed cerebrovascular hyperpermeability.
• sEVs from diabetic mice and humans increased in quantity and size.
• Diabetic sEVs disrupted endothelial cell barriers by modulating MEK/ROCK pathways and cell-cell junctions.

Conclusions:

• Diabetes increases circulating sEV concentration and size.
• Diabetic sEVs induce vascular leak via MEK/ROCK pathway activation.
• sEVs may play a role in diabetic cerebrovascular dysfunction and cognitive decline.