The redox balance (balance of reduction and oxidation reactions in blood) is essential for healthy circulation. Redox imbalance causes alterations of protein function contributing to the development of thrombosis. Our Group is focused on redox modification of disulphide bonds in two proteins critical for thrombus formation: the platelet receptor integrin a2bb3 and the plasma protein von Willebrand factor (vWF). We have found that reduced forms of a2bb3 and vWF have decreased thrombotic activity and may therefore protect from thrombotic disease, such as venous clots.
We have developed assays that measure the redox balance in blood, including tests which measure the disulphide reducing activity of plasma and the production of reactive oxygen species by platelets. We will study the redox modifications of platelet a2bb3 and plasma vWF that occur in patients at high risk for thrombosis to identify those most likely to benefit from drugs which restore the normal redox balance.