Triglycerides and the fibrinolytic system

In a previous study we have shown that in patients with diagnosis of type IV hyperlipoproteinemia plasma levels of both tissue type plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) are elevated. In addition in the same study a direct correlation between plasma triglyceride levels and PAI-1 has been observed . In an attempt to elucidate the mechanisms responsible for the increased levels of PAI-1 observed in hypertriglyceridemia, a series of in vitro experiments were thus performed. VLDL in vitro concentration-dependently increased the synthesis and the release of PAI-1 by human umbilical vein endothelial cells and by hepatic cells (HepG2). The mechanism of action of VLDL on PAI- 1 synthesis was further investigated in HepG2 cells. The results indicate that VLDL increase the expression of PAI-1 mRNA by HepG2 cells, with an effect more pronounced on the 2.2 Kb PAI-1 mRNA species. In addition the effect of VLDL on both the synthesis of PAI-1 antigen and on the expression of PAI-1 mRNA is further increased by the coincubation with insulin (135 nM) in the conditioned medium.