Details

Autor(en) / Beteiligte

• Nordt, T K
• Lutzi, S
• Ruef, J
• Peter, K
• Klar, E
• Kübler, W
• Sobel, B E
• Bode, C

Titel

Attenuation by fibrates of plasminogen activator inhibitor type-1 expression in human arterial smooth muscle cells

Ist Teil von

• Thrombosis and haemostasis, 2001-11, Vol.86 (5), p.1305-1313

Ort / Verlag

Germany

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• Human atherosclerotic lesions exhibit increased expression of plasminogen activator inhibitor type-1 (PAI-1) that has been implicated in atherogenesis. Although vascular smooth muscle cells are a predominant source of PAI-1 expression potentially favorable modulation of PAI-1 expression by fibrates has not yet been characterized in these cells. Human aortic smooth muscle cells were exposed to selected growth factors. PAI-1 expression was stimulated most powerfully by TGF-beta (EC50 = 0.2 ng/ml, up to 12-fold increase). Gemfibrozil inhibited basal PAI-1 expression by 23% (p = ns) and TGF-beta-induced PAI-1 expression by 52% (p = 0.017) whereas t-PA and total protein synthesis was not affected. Changes in PAI-1 protein accumulation reflected PAI-1 gene expression attributable to modulation of half-life of PAI-1 mRNA by gemfibrozil. Inhibition by other fibrates was less. Gemfibrozil specifically attenuates TGF-beta-induced PAI-1 expression in human arterial smooth muscle cells. Thus, fibrates are promising agents for normalizing increased PAI-1 expression in arterial walls in patients in whom PAI-1 expression is increased.