Plasminogen activator inhibitor-1 and haemostasis in obesity

The connection between obesity and disordered haemostasis is well establish ed, but incompletely understood. There is a strong link between inhibition of fibrinolysis and obesity, and elevation of the plasma inhibitor, plasmin ogen activator inhibitor-1 (PAI-1), is regarded as a central factor. Here w e explore the increased risk of atherothrombotic disorders in obese subject s, and the evidence for metabolic and genetic causes. There is a clear rela tionship between plasma PAI-1 and obesity, and adipose tissue synthesises P AI-1, as has been shown in mouse and rat models, and more recently in human material. This tissue also produces several effector molecules that can up regulate PAI-1. These molecules include transforming growth factor beta, t umour necrosis factor a, angiotensin II and interleukin 6, all of which up regulate PAI-1 in various cell types. The issue of whether adipose tissue d irectly contributes to plasma PAI-1, or whether it primarily contributes in directly, its products stimulating other cells to produce PAI-1 that feeds into the plasma pool, is not yet resolved. Finally, we briefly examine othe r proteins of haemostasis that are products of adipose tissue. Further stud ies are needed to define the regulation of these proteins, in adipose tissu e itself and in other cells influenced by its products, in order to extend recent insights into the links between obesity and haemostasis.