Plasminogen activator inhibitor-1 and haemostasis in obesity.
The connection between obesity and disordered haemostasis is well established, but incompletely understood. There is a strong link between inhibition of fibrinolysis and obesity, and elevation of the plasma inhibitor, plasminogen activator inhibitor-1 (PAI-1), is regarded as a central factor. Here we explore the increased risk of atherothrombotic disorders in obese subjects, and the evidence for metabolic and genetic causes. There is a clear relationship between plasma PAI-1 and obesity, and adipose tissue synthesises PAI-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, tumour necrosis factor alpha, angiotensin II and interleukin 6, all of which up regulate PAI-1 in various cell types. The issue of whether adipose tissue directly contributes to plasma PAI-1, or whether it primarily contributes indirectly, its products stimulating other cells to produce PAI-1 that feeds into the plasma pool, is not yet resolved. Finally, we briefly examine other proteins of haemostasis that are products of adipose tissue. Further studies are needed to define the regulation of these proteins, in adipose tissue itself and in other cells influenced by its products, in order to extend recent insights into the links between obesity and haemostasis.
Mutch
N J
NJ
Institute of Medical Sciences, University of Aberdeen, UK.
Wilson
H M
HM
Booth
N A
NA
D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D005342:Fibrinolysis; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D009765:Obesity / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1