Attenuation by Fibrates of Plasminogen Activator Inhibitor Type-1 Expression in Human Arterial Smooth Muscle Cells Academic Article uri icon

abstract

  • SummaryHuman 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-β (EC50 = 0.2 ng/ml, up to 12-fold increase). Gemfibrozil inhibited basal PAI-1 expression by 23% (p = ns) and TGF-β -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-β -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.

authors

  • Lutzi, Steffen
  • Ruef, Johannes
  • Peter, Karlheinz
  • Klar, Ernst
  • Kübler, Wolfgang
  • Sobel, Burton
  • Bode, Christoph
  • Nordt, Thomas

publication date

  • 2001