Thromb Haemost 2003; 90(01): 36-42
DOI: 10.1055/s-0037-1613596
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Independence of growth factor induced plasminogen activator inhibitor type-1 (PAI-1) expression from the 4G/5G polymorphism of the PAI-1 gene

Thomas K. Nordt
1   Department of Cardiology, University of Freiburg, Germany
,
Esther Eschenfelder
1   Department of Cardiology, University of Freiburg, Germany
,
Karlheinz Peter
1   Department of Cardiology, University of Freiburg, Germany
,
Burton E. Sobel
1   Department of Cardiology, University of Freiburg, Germany
,
Christoph Bode
1   Department of Cardiology, University of Freiburg, Germany
› Author Affiliations
Financial support: This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG NO214/2-1), by a grant from the Medizinische Fakultät Heidelberg (178/97), and by a grant from the Zentrum für Klinische For-schung II (Herz- und Gefäßkrankheiten), Universitätsklinikum Freiburg (ZKFII-D3)
Further Information

Publication History

Received 17 June 2002

Accepted after resubmission 24 March 2003

Publication Date:
07 December 2017 (online)

Summary

Increased PAI-1 expression has been implicated in accelerating atherogenesis. Increases under some conditions are modulated by growth factors. Genetic factors such as the 4G/5G poly-morphism in the promoter of the PAI-1 gene play a role under certain circumstances. The present study was designed to delineate for the first time interactions between growth factors and the 4G/5G polymorphism with respect to PAI-1 expression in human arterial smooth muscle cells (HASMC).

HASMC were genotyped and exposed to growth factors. PAI-1 gene and protein expression were induced consistently by TGF-β (up to 4.0-fold), PDGF (2.1-fold),TNF-α (1.7-fold), and thrombin (2.3-fold). Results were similar regardless of which genotype (4G/4G [n=9], 4G/5G [n=13], and 5G/5G [n=7]) was present.

The induction of increased PAI-1 expression in human arterial smooth muscle cells by growth factors implicated in accelerated atherogenesis is independent of the PAI-1 4G/5G polymorphism. Accordingly, modulation of PAI-1 expression is likely to be influenced predominantly by environmental factors acting on, rather than genetic factors intrinsic to the PAI-1 promoter.

 
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