Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue.

Abstract

Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels of PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.

• Authors: Mattias Ekström, Jan Liska, Per Eriksson, Eva Sverremark-Ekström, Per Tornvall
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 108 Issue 3 Pg. 485-92 (Sep 2012) ISSN: 2567-689X [Electronic] Germany
• PMID: 22740034 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• DNA, Complementary
• IL6 protein, human
• Interleukin-6
• Plasminogen Activator Inhibitor 1
• RNA, Messenger
• SERPINE1 protein, human
• Tissue Plasminogen Activator

Topics

• Abdominal Fat (metabolism)
• Acute Disease
• Adrenergic beta-Antagonists (pharmacology)
• Aged
• Aged, 80 and over
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Coronary Artery Bypass
• DNA, Complementary (genetics)
• Fibrinolysis (physiology)
• Gene Expression Regulation (drug effects)
• Heart Valve Prosthesis Implantation
• Humans
• Immunoenzyme Techniques
• Inflammation (genetics, metabolism)
• Interleukin-6 (biosynthesis, genetics)
• Male
• Middle Aged
• Omentum (metabolism)
• Plasminogen Activator Inhibitor 1 (biosynthesis, genetics)
• Postoperative Complications (genetics, metabolism)
• RNA, Messenger (biosynthesis, genetics)
• Subcutaneous Fat (metabolism)
• Tissue Plasminogen Activator (biosynthesis, genetics)