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Plasminogen activator inhibitor-1 and haemostasis in obesity

Published online by Cambridge University Press:  05 March 2007

Nicola J. Mutch ,
Heather M. Wilson  and
Nuala A. Booth
Nicola J. Mutch
Affiliation:
Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
Heather M. Wilson
Affiliation:
Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
Nuala A. Booth*
Affiliation:
Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
*
*Corresponding author: Dr Nuala Booth, fax +44 1224 273144, email [email protected]
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Abstract

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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 b, tumour 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 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.

Keywords

ObesityPAI-1ThrombosisInsulin resistanceCardiovascular disease
Type
Symposium on ‘New perspectives on adipose tissue function’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 3 , August 2001 , pp. 341 - 347
Copyright
Copyright © The Nutrition Society 2001

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