Thromb Haemost 2008; 100(06): 992-1006
DOI: 10.1160/TH08-07-0490
Theme Issue Article
Schattauer GmbH

Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: Lessons from the liver

Elitsa Y. Dimova
1   Department of Chemistry/Biochemistry, University of Kaiserslautern, Kaiserslautern, Germany
,
Thomas Kietzmann
1   Department of Chemistry/Biochemistry, University of Kaiserslautern, Kaiserslautern, Germany
› Author Affiliations
Further Information

Publication History

Received: 30 July 2008

Accepted after major revision: 12 September 2008

Publication Date:
23 November 2017 (online)

Summary

Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are found in PAI-1 patients with type 2 diabetes mellitus which is associated with a dysbalance in glucose and lipid homeostasis. Especially a defective insulin response in the liver contributes to the development of hyperglycemia, dyslipidemia and peripheral insulin resistance and may contribute to hepatic overexpression of PAI-1 in diabetes type 2. Furthermore,a substantial upregulation of PAI-1 expression has also been shown in a variety of liver injury models.Thus, the liver appears to be not only a major site of PAI-1 synthesis in response to hormonal changes, but also in response to a variety of other pathological events. PAI-1 expression in liver largely depends on activation of signalling pathways and transcriptional regulators which may be the basis fora new level of cross-talk between different signalling pathways and thus may represent attractive therapeutic candidates.This article will primarily focus on the regulation of PAI-1 expression in liver cells and discuss potential cross-talks between metabolic, hormonal and environmental signals.

 
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