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Circulating small extracellular vesicles mediate vascular hyperpermeability in diabetes – published online 15/03/2024

Gustafson graphical abstract

Dakota Gustafson, Peter V. DiStefano, Xue Fan Wang, Ruilin Wu, Siavash Ghaffari, Crizza Ching, Kumaragurubaran Rathnakumar, Faisal Alibhai, Michal Syonov, Jessica Fitzpatrick, Emilie Boudreau, Cori Lau, Natalie Galant, Mansoor Husain, Ren‑Ke Li, Warren L. Lee, Rulan S. Parekh, Philippe P. Monnier, Jason E. Fish

While vascular leakiness is a prominent feature of diabetes, the mechanisms are poorly understood. Of particular concern is leak in the brain, as this is associated with cognitive impairment. In this issue, Gustafson and DiStefano et al (–024–06120–9) report that circulating small extracellular vesicles contribute to cerebrovascular leak in type 2 diabetes. The authors found that the abundance of circulating extracellular vesicles is increased in diabetes and that the proteins present in these vesicles are altered. Using intravital microscopy, they show that injection of extracellular vesicles isolated from a mouse model of type 2 diabetes into non-diabetic mice can induce cerebrovascular leak. Mechanistically, these vesicles increase transcytosis and disrupt cell–cell junctions in endothelial cells, and the vascular leak is dependent on MAPK/Rho-associated protein kinase (ROCK) signalling. The authors conclude that these findings provide insights into circulating factors that drive vascular leakiness in type 2 diabetes and suggest new therapeutic approaches to prevent vascular complications, including cognitive impairment.

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