The behaviour of BH4 in cardiovascular disease: friend or foe?

Cell-specific roles for tetrahydrobiopterin in cardiovascular disease pathogenesis (renewal: years 11-15)

Researchers know that a molecule called BH4 is very important to the circulatory system. However it appears to have two opposing functions. High levels of BH4 in cells that line blood vessels (endothelial cells) protect against disease by helping to maintain the blood vessel’s structure and function. However this same molecule is also thought to contribute to the development of dangerous fatty plaques in the blood vessel wall by its activity in the body’s immune cells. This dual nature of BH4 function has made it difficult to understand its behaviour in the body and how this may be manipulated to develop new ways to prevent or treat heart disease. Professor Keith Channon and his team are investigating the behaviour of BH4 in endothelial cells and immune cells. Identifying its differing actions in each cell type will clarify the effect of BH4 on the development of diseases such as high blood pressure and plaque build-up in the artery wall. Genetically modified mice will be used to study the functions of BH4, and how it could be used as a basis for treatment.