Dr Alan Stewart and Prof Ramzi Ajjan (University of Leeds) have just been awarded a BHF PhD studentship grant of £108k for a project entitled “Plasma non-esterified fatty acids and fibrin clot formation in obesity – a relationship forged in zinc?“. The grant will provide funding for Stephen Hierons.
Zn2+ is an essential regulator of coagulation and its availability in plasma is fine-tuned through buffering by human serum albumin (HSA). Non-esterified fatty acids (NEFAs) transported by HSA reduce its ability to bind/buffer Zn2+. It is thought that this occurs through binding to HSA at a particular NEFA site called FA2. This dynamic is important as plasma NEFA levels are elevated in type-2 diabetes mellitus (T2DM), obesity and other disorders that associate with an increased risk of developing thrombotic complications. Through our previous work we found that only certain plasma NEFAs are elevated in T2DM/obese subjects (compared to leaner controls without diabetes) and their levels correlate with fibrin clot parameters.
Here we will identify the role of the FA2 site in mediating Zn2+-mishandling by HSA and will assess the degree to which individual NEFAs enhance Zn2+-dependent effects on fibrin clot formation and lysis. Finally we will examine whether bariatric surgery, which is known to lower plasma NEFA concentrations in obese individuals (by restricting calorie intake), beneficially influences fibrin clot formation and lysis in obese individuals. Collectively, the work will provide essential information relating to the interplay between plasma NEFAs and a key coagulatory pathway in obesity.