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Thomas K. Nordt, Esther Eschenfelder, Karlheinz Peter, Burton E. Sobel, Christoph Bode
Independence of growth factor induced plasminogen activator inhibitor type-1 (PAI-1) expression from the 4G/5G polymorphism of the PAI-1 gene
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 polymorphism 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- (up to 4.0-fold), PDGF (2.1-fold), TNF- (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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 90, 07/2003
Pages: 36 - 42