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June 2022


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A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth. DZHK authors: Marco Castro, Toshiya Sugino, Kerstin Wilhelm, Stefan Guenther, André Schneider, Thomas Braun, Holger Gerhardt, Michael Potente, Nature Metabolism, 2022, DOI 10.1038/s42255-022-00584-y

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Blood vessels must adapt their growth to the nutrients available in their surroundings to keep organs adequately supplied. A team led by Michael Potente has identified two essential proteins for this process and published their findings in "Nature Metabolism".

Blood vessels run throughout the human body and ensure that the organs get all the necessary nutrients and oxygen. If these networks stop working as they should, diseases develop. While age-related cardiovascular conditions frequently cause vessels to atrophy, malignant tumours are characterized by excessive growth of misrouted vessels. Wet macular degeneration is also associated with sprouting new blood vessels in the wrong place. At its worst, the condition can cause blindness.

To develop targeted therapies for these diseases, the researchers want to find out how exactly the growth of new blood vessels, the angiogenesis, is regulated within the body. They report that the proteins  YAP and TAZ play a crucial role in allowing vessels to sprout, even under challenging metabolic conditions. The proteins are part of the Hippo signalling pathway, which regulates organ growth and size in almost all living things. If these two molecules are active in the endothelial cells, they read genes that lead to increased growth of specific surface transporters.

These allow the vessel cells to absorb more essential nutrients for growth and cell division. YAP and TAZ, which both function similarly, act as a kind of door-opener.

The increased absorption of nutrients then activates another protein, called mTOR. mTOR is a critical control point in the cells that triggers growth and cell division. This allows new blood vessel networks to expand. However, the researchers do not yet know which signals regulate the activity of YAP and TAZ in endothelial cells.

The findings are based on mouse experiments, as the mouse retina is an ideal model for studying blood vessel development. "Using genetically modified mouse lines, we showed how endothelial cells that don't produce YAP and TAZ rarely divide," says Potente. This inhibited vessel growth in the mice. The TAZ protein plays a significant role in this process, while YAP is the decisive factor in most other cell types

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