New map reveals that blood vessels play an active role in disease

Adipose tissue is far more important for our health than many may realise. It does not merely function as an energy store, but as an active tissue that continuously communicates with the rest of the body. This communication requires a dense network of blood vessels, which supply nutrients and help regulate the body’s immune system.

The new study, recently published in Nature Metabolism, shows that the network of blood vessels changes markedly in obesity and type 2 diabetes and that the blood vessels themselves appear to be linked to mechanisms that drive disease.

“Our results suggest that blood vessels do not only respond to disease but may also play an active role in the processes underlying it,” says Joanna Maria Kalucka, Associate Professor at the Department of Biomedicine at Aarhus University, who led the study.

A hidden and complex system

The researchers analysed nearly 70,000 cells from blood vessels in adipose tissue from 65 individuals using advanced methods that allow cells to be examined individually. This provides a far more detailed picture than previously possible.

The analysis shows that blood vessels consist of several different types of endothelial cells, which are the cells that line the interior of blood vessels. Each cell type appears to have its own specialised function.

“From our previous work, we knew that endothelial cells are not all the same, but the full extent of their diversity in human adipose tissue had not yet been explored,” says Joanna Maria Kalucka.

Blood vessels change character in disease

When the researchers compared healthy individuals with those with obesity and type 2 diabetes, they observed clear differences.

In disease states, the cells of the blood vessels change and begin to exhibit properties that promote inflammation and tissue damage. That is two key mechanisms in the development of metabolic diseases.

“We find that blood vessels are not only affected by disease but may also play a role in shaping its development,” says Joanna Maria Kalucka.

Discovery of a new and unusual cell type

The researchers also identified something not previously observed: a group of cells with mixed characteristics.

This group shares features with vascular cells, adipocytes, connective tissue cells and immune cells – cell types that normally have very different functions in the body.

The finding suggests that some cells in blood vessels appear able to change their characteristics and adapt to their surroundings.

“This indicates that the cells are more flexible and adaptable than we have previously believed, and this may be important for how disease arises,” says Joanna Maria Kalucka.

Providing researchers with a new tool

The results indicate that blood vessels may represent an important and previously overlooked therapeutic target.

Currently, treatment of obesity and type 2 diabetes primarily focuses on metabolism and hormones. However, the new findings suggest that vascular function also plays a central role.

“If we can understand and influence the changes occurring in blood vessels, this could, in the long term, open up new ways of treating these diseases,” says Joanna Maria Kalucka.

The researchers have also made their data available as an open, interactive atlas for other scientists to use. This enables researchers worldwide to explore how cells behave in both healthy and diseased tissue.

The next step is to investigate how the newly discovered cell types arise and what role they play in disease development.

“Now we need to understand how this knowledge can be used to improve human health,” says Joanna Maria Kalucka.

About the research project

• Study type: Basic research based on human tissue samples, combining single-cell RNA sequencing, computational analysis and imaging
• Collaborators: Aarhus University and Steno Diabetes Center Aarhus, in collaboration with international research institutions including Helmholtz Zentrum München, Karolinska Institutet and Harvard Medical School
• Funding: Lundbeck Foundation, Carlsberg Foundation, AUFF and the Riisfort Foundation
• Conflicts of interest: The researchers report no conflicts of interest
• Published in: Nature Metabolism
• Read the scientific article: “Defining the vascular niche of human adipose tissue across metabolic states” 

Contact

Associate Professor Joanna Maria Kalucka
Aarhus University, Department of Biomedicine
Email: joanna.kalucka@biomed.au.dk