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-beta (up to 4.0-fold), PDGF (2.1-fold), TNF-alpha (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.
Nordt
Thomas K
TK
Department of Cardiology, University of Freiburg, Germany. t.nordt@katharinenhospital.de
Eschenfelder
Esther
E
Peter
Karlheinz
K
Sobel
Burton E
BE
Bode
Christoph
C
D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D006133:Growth Substances / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D006133:Growth Substances; D017395:Plasminogen Activator Inhibitor 1; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator