Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in HepG2 cells

The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR ga mma activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in HepG2 cells were investigated. Exposure of the cells for 24 hour s to either oleic acid or insulin showed no obvious effects on PAI-1 synthe sis, whereas the combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis, which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of PAI-1 mRNA. This up-regulation of PAI-1 synthesi s was attenuated by bezafibrate in a dose-dependent manner (1-100 muM) with 30 % reversal at 100 muM. In contrast, troglitazone further stimulated PAI -1 synthesis to 140 % of the level obtained in the presence of both oleic a cid and insulin. This attenuation by bezafibrate and enhancement by troglit azone required the presence of both oleic acid and insulin. It is interesti ng that PAI-1 expression was affected so differently by these two PPAR acti vators. (C) 2001 Elsevier Science Inc. All rights reserved.