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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:89-96.)
© 1996 American Heart Association, Inc.

Articles

Plasminogen Activator Inhibitor Type-1 Synthesis and mRNA Expression in HepG2 Cells Are Regulated by VLDL

Luigi Sironi; Luciana Mussoni; Livia Prati; Damiano Baldassarre; Marina Camera; Cristina Banfi; Elena Tremoli

From the Institute of Pharmacological Sciences and E. Grossi Paoletti Center (D.B.), University of Milan, Italy.

Abstract The effect of VLDL on plasminogen activator inhibitor type 1 biosynthesis in HepG2 cells was investigated. Exposure of HepG2 cells to VLDL (range, 10 to 100 µg protein per milliliter) for 16 hours resulted in an enhanced release of PAI-1 antigen and PAI activity into conditioned medium, accompanied by the accumulation of intracellular triglycerides. By using a monoclonal antibody (IgG C7) specific to the LDL receptor, we showed that the effect of VLDL is mediated by its interaction with the LDL receptor. Enhanced PAI-1 release was due to increased biosynthesis: 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 insulin with the VLDL further enhanced PAI-1 antigen release and PAI-1 mRNA accumulation. The effect of VLDL on steady state levels of PAI-1 mRNA was apparently not due to an increase of gene transcription but to stabilization of both PAI-1 mRNA transcripts. The enhancing effect of VLDL 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.

Key Words: VLDL • plasminogen activator inhibitor type-1 • HepG2 • gene expression • insulin

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