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Thromb Haemost 2004; 91(04): 674-682
DOI: 10.1160/TH03-06-0384
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidinediones

Andreas Zirlik
1   Department of Cardiology, University of Freiburg, Freiburg, Germany
,
Anne Leugers
1   Department of Cardiology, University of Freiburg, Freiburg, Germany
,
Jens Lohrmann
1   Department of Cardiology, University of Freiburg, Freiburg, Germany
,
Sandra Ernst
1   Department of Cardiology, University of Freiburg, Freiburg, Germany
,
Burton E. Sobel
2   Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA
,
Christoph Bode
1   Department of Cardiology, University of Freiburg, Freiburg, Germany
,
Thomas K. Nordt
1   Department of Cardiology, University of Freiburg, Freiburg, Germany
3   Department of Cardiology, Katharinenhospital, Klinikum Stuttgart, Stuttgart, Germany
› Author AffiliationsFinancial support: The present study was supported by a grant from Astra Zeneca (to T.K.N.).
Further Information

Publication History

Received 19 June 2003

Accepted after revision 21 January 2004

Publication Date:
06 December 2017 (online)

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Summary

Adipose tissue produces substantial amounts of plasminogen activator inhibitor type-1 (PAI-1), an established cardiovascular risk factor. This study evaluated PAI-1 expression in human adipose tissue in response to thiazolidinediones, insulin sensitising drugs activating peroxisome proliferator-activated receptorgamma (PPAR-γ). Troglitazone, rosiglitazone, and ciglitazone significantly reduced PAI-1 protein expression in human preadipocytes under basal conditions and after stimulation of the cells with TGF-β. Pioglitazone had no effect. In human adipocytes all four thiazolidinediones significantly attenuated PAI-1 expression. Signalling appeared to be mediated via PPAR-γ and effects reflected, at least in part, changes in transcription. Accordingly, patients with insulin resistance may benefit from treatment with thiazolidinediones with respect to diminution of PAI-1 expression in adipose tissue and consequent potential reduction of cardiovascular risk.

Keywords

PAI-1 - adipose tissue - PPAR-γ - coronary heart disease - diabetes mellitus
 

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