Effects of triglyceride rich lipoproteins on the synthesis of plasminogen activator inhibitor 1 (PAI-1) by HepG2 cells

In this study the effects of very low density lipoproteins (VLDL) isolated from plasma of normal donors on PAI-1 synthesis by HepG2 cells were evaluated. To this end confluent HepG2 cells were incubated for 14-16 hours with serum free medium in the presence and in the absence of different concentrations of VLDL. VLDL (25-200 mg protein/mI) concentration-dependently increased the release of PAI-1 by the cells. The increases in PAI-1 synthesis observed in the presence of VLDL were accompanied by concomitant changes in PA-1 mRNA levels as determined by Northern blot analysis. In the presence of 100 mg/ml VLDL the cellular levels of the 2.2 Kb PAI-1 mRNA species were increased by threefold (p<0.001, n=7), whereas levels of the 3.2 Kb PAI-1 mRNA remained essentially unchanged or even decreased. Time-course experiments showed that the effects of VLDL on the 2.2 Kb PAI-1 mRNA were evident after 9 hour incubation of the lipoproteins with cells. A concentration of insulin (135 nM) known to increase PAI-1 synthesis in this cell type exerted additive effects to VLDL on both PAI-1 antigen and PAI-1 mRNA expression. It is concluded that triglyceride rich lipoproteins increase PAI-1 synthesis by HepG2 cells, an effect that may further enhanced by insulin.