Investigating a potential link between diabetes and damage to blood vessels

The role and regulation of DNA cytosine demethylases in hyperglycaemia-induced endothelial dysfunction

Diabetes is a condition where the body can’t produce enough or respond properly to insulin, a hormone that controls blood glucose (sugar) levels. If these levels are not well controlled, it can have serious consequences - including damage to blood vessels. But exactly how high glucose levels cause this damage is not fully understood. The walls of our blood vessels are lined by endothelial cells, which form a barrier that allows the controlled movement of substances, such as glucose, between the blood and the other body tissues. The ability of these cells to function properly relies on being able to precisely switch the relevant genes on and off as required. A group of enzymes, called TETs, can provide these ‘switches’ by chemically modifying genes in response to specific signals. In this project, Dr Alison Brewer and her team are studying the potential link between the activity of TETs and the function of endothelial cells exposed to high glucose levels. They will also test whether a compound known to help maintain endothelial function, called ascorbic acid, has this effect due to altering TET activity. Millions of people in the UK and worldwide are living with diabetes – putting them at risk of many other dangerous heart and circulatory diseases. This research could help advance our understanding of how diabetes damages blood vessels, and could pave the way for further studies exploring the potential use of treatments targeting TETs to limit these effects.