Understanding the roles of the regulatory enzymes DDAH in the brain’s circulation

Defining the roles of dimethylarginine dimethylaminohydrolases (DDAH) in cerebrovascular regulation (Mr Arun Flynn)  

This team is addressing a gap in knowledge about blood vessel health in the brain, hoping to identify new ways to tackle diseases such as stroke. The health and function of our blood vessels is highly influenced by the layer of cells lining the vessel, called the endothelium. One very important molecule produced by the endothelium is nitric oxide, which is crucial in blood vessel function. A substance known as ADMA – made by all cells in the body – blocks the production of nitric oxide in blood vessels. High levels of ADMA have been linked to brain diseases such as stroke. ADMA has a number of damaging effects in the body. It is therefore kept under strict control by enzymes known as DDAH. DDAH enzymes are important for preserving the health of blood vessels around the body but very little is known about how ADMA and DDAH work in brain blood vessels. This project will begin to address this lack of understanding. Using genetically modified mice that lack the DDAH enzymes, the team will determine how important these enzymes are for maintaining healthy brain blood vessels in normal conditions and after a stroke. This could lead to new medicines for the treatment of brain diseases, such as stroke.