New mechanism behind vascular damage in type 2 diabetes identified
Researchers at Karolinska Institutet have discovered a new mechanism behind blood vessel damage in type 2 diabetes. The study, published in the Journal of Clinical Investigation, shows that small vesicles from red blood cells can transfer harmful signal molecules to the blood vessels and impair their function.
Blood vessel damage is a common complication in type 2 diabetes and can lead to cardiovascular diseases such as heart attack and stroke. Despite the known link between diabetes and vascular problems, the underlying mechanisms have been incompletely understood. A new study from Karolinska Institutet shows that extracellular vesicles – small membrane bubbles – released from red blood cells can contribute to blood vessel damage.
“We have seen that vesicles from red blood cells in patients with type 2 diabetes are taken up by endothelial cells in blood vessels to a greater extent than in healthy individuals”, says John Pernow, professor at the Department of Medicine, Solna and lead author of the study.
The research group analyzed blood samples from patients with type 2 diabetes and compared them with samples from healthy control subjects. They isolated the vesicles and examined their contents as well as their impact on blood vessels from both humans and mice. The results showed that a specific signaling molecule, arginase, is transported with the vesicles and causes the formation of harmful free oxygen radicals in the blood vessel wall. This impairs the blood vessels' ability to dilate, which in turn can contribute to the vascular complications seen in diabetes.
The study also showed that it is possible to counteract the harmful effects by inhibiting the uptake of vesicles in the blood vessels and blocking arginase activity and the formation of oxygen radicals.
“Our results provide a new understanding of how red blood cells contribute to vascular damage in type 2 diabetes and point to possible treatment strategies to counteract these complications,” says first author Aida Collado Sánchez at the same institution.
The next step in the research will be to investigate whether similar changes occur in the blood circulation of patients and to map more signaling molecules transferred with the vesicles. The researchers also plan to test new drug candidates that can block vesicle uptake and counteract the negative effects of harmful signaling molecules.
The study was conducted in collaboration with Karolinska University Hospital and funded by, among others, the Swedish Heart-Lung Foundation, the Swedish Research Council, and the Knut and Alice Wallenberg Foundation.
Publication
Erythrocyte-derived extracellular vesicles induce endothelial dysfunction through arginase-1 and oxidative stress in type 2 diabetes.
Collado A, Humoud R, Kontidou E, Eldh M, Swaich J, Zhao A, Yang J, Jiao T, Domingo E, Carlestål E, Mahdi A, Tengbom J, Végvári Á, Deng Q, Alvarsson M, Gabrielsson S, Eriksson P, Zhou Z, Pernow J
J Clin Invest 2025 Mar;():