Very low density lipoprotein-mediated signal transduction and plasminogen activator inhibitor type 1 in cultured HepG2 cells

Cristina Banfi, Luciana Mussoni, Patrizia Risé, Maria Grazia Cattaneo, Lucia Vicentini, Fiorenzo Battaini, Claudio Galli, Elena Tremoli

Research output: Contribution to journalArticlepeer-review

Abstract

In normal subjects and in patients with cardiovascular disease, plasma triglycerides are positively correlated with plasminogen activator inhibitor type 1 (PAI-1) levels. Moreover, in vitro studies indicate that VLDLs induce PAI-1 synthesis in cultured cells, ie, endothelial and HepG2 cells. However, the signaling pathways involved in the effect of VLDL on PAI-1 synthesis have not yet been investigated. We report that VLDLs induce a signaling cascade that leads to an enhanced secretion of PAI-1 by HepG2 cells. In myo- [3H]inositol-labeled HepG2 cells, VLDL (100 μg/mL) caused a time-dependent increase in [3H]inositol phosphates, the temporal sequence being tris>bis>monophosphate. VLDL brought about a time-dependent stimulation of membrane-associated protein kinase C (PKC) activity and arachidonate release. Finally, VLDL stimulated mitogen-activated protein (MAP) kinase, and this effect was reduced by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), which suggests that PKC plays a pivotal role in MAP kinase phosphorylation. VLDL-induced PAI-1 secretion was completely prevented by U73122, a specific inhibitor of phosphatidylinositol-specific phospholipase C, by H7 or by PKC downregulation, and by mepacrine (all P2+ release from intracellular stores, inhibited VLDL-induced PAI-1 secretion by 60% (P

Original languageEnglish
Pages (from-to)208-217
Number of pages10
JournalCirculation Research
Volume85
Issue number2
Publication statusPublished - Jul 23 1999

Keywords

  • Fibrinolysis
  • Hepatoma cell line
  • Plasminogen activator inhibitor type 1
  • Signaling
  • VLDL

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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