PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 SYNTHESIS AND MESSENGER-RNA EXPRESSION IN HEPG2 CELLS ARE REGULATED BY VLDL

The effect of VLDL on plasminogen activator inhibitor type 1 biosynthe sis in HepG2 cells was investigated. Exposure of HepG2 cells to VLDL ( range, 10 to 100 mu g protein per milliliter) for 16 hours resulted in an enhanced release of PAI-1 antigen and PAT activity into conditione d medium, accompanied by the accumulation of intracellular triglycerid es. By using a monoclonal antibody (IgG C7) specific to the LDL recept or, we showed that the effect of VLDL is mediated by its interaction w ith the LDL receptor. Enhanced PAT-1 release was due to increased bios ynthesis: PAI 1 mRNA was doubled, mainly because of the effect on the 2.2-kb PAI-1 mRNA rather than the 3.2-kb transcript. Addition of insul in with the VLDL further enhanced PAI-1 antigen release and PAI-1 mRNA accumulation. The effect of VLDL on steady stale levels of PAI-1 mRNA was apparently not due to an increase of gene transcription but to st abilization of both PAI-1 mRNA transcripts. The enhancing effect of VL DL on PAI-1 biosynthesis in HepG2 cells may raise PAI-1 antigen levels not only in hypertriglyceridemic states but also in those conditions in which both insulin and VLDL are elevated.