Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1.

Abstract

Obesity is the central promoter of the metabolic syndrome which also includes disturbed fibrinolysis in addition to hypertension, dyslipidaemia and impaired glucose tolerance/type 2 diabetes mellitus. Plasminogen activator inhibitor-1 (PAI-1) is the most important endogenous inhibitor of tissue plasminogen activator and uro-plasminogen activator, and is a main determinant of fibrinolytic activity. There is now compelling evidence that obesity and, in particular, an abdominal type of body fat distribution are associated with elevated PAI-1 antigen and activity levels. Recent studies established that PAI-1 is expressed in adipose tissue. The greater the fat cell size and the adipose tissue mass, the greater is the contribution of adipose production to circulating PAI-1. Experimental data show that visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue. Studies in human adipocytes indicate that PAI-1 synthesis is upregulated by insulin, glucocorticoids, angiotensin II, some fatty acids and, most potently, by cytokines such as tumour necrosis factor-alpha and transforming growth factor-beta, whereas catecholamines reduce PAI-1 production. Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT(1)-receptor antagonists were found to reduce adipose expression of PAI-1. In addition, weight loss by dietary restriction or comprehensive lifestyle modification is effective in lowering PAI-1 plasma levels. In conclusion, impaired fibrinolysis in obesity is probably also due to an increased expression of PAI-1 in adipose tissue. An altered function of the endocrine system and an impaired auto-/paracrine function at the fat cell levels may mediate this disturbance of the fibrinolytic system and thereby increase the risk for cardiovascular disease..

• Authors: T Skurk, H Hauner
• Journal: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity (Int J Obes Relat Metab Disord) Vol. 28 Issue 11 Pg. 1357-64 (Nov 2004) England
• PMID: 15356668 (Publication Type: Journal Article, Review)

Chemical References

• Cytokines
• Hypoglycemic Agents
• Insulin
• Plasminogen Activator Inhibitor 1

Topics

• Adipocytes (metabolism, pathology)
• Adipose Tissue (metabolism, pathology)
• Cytokines (blood)
• Fibrinolysis
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (blood)
• Metabolic Syndrome (blood)
• Obesity (blood, drug therapy, pathology)
• Plasminogen Activator Inhibitor 1 (biosynthesis, metabolism)
• Risk