Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein

Arteriosclerosis. 1990 Nov-Dec;10(6):1067-73. doi: 10.1161/01.atv.10.6.1067.

Abstract

Clinical studies have demonstrated an impaired fibrinolytic function in patients with angiographically ascertained coronary artery disease or previous myocardial infarction. This decreased fibrinolytic function is to a major extent explained by the presence of high plasma levels of plasminogen activator inhibitor-1 (PAI-1) and is most common in patients with hyperlipoproteinemias type IIB and IV. To further investigate the association between hypertriglyceridemia and elevated plasma levels of PAI-1, cultured human umbilical vein endothelial cells were exposed to purified lipoproteins isolated from normo- and hypertriglyceridemic (NTG and HTG) individuals. We found that very low density lipoprotein (VLDL) from both NTG and HTG subjects stimulated the secretion of PAI-1 from endothelial cells in a dose-dependent manner. HTG-VLDL at a concentration of 100 micrograms/ml gave rise to a 73% increase in PAI-1 secretion as compared to control cultures, whereas NTG-VLDL only gave rise to a 30% increase (p less than 0.05), indicating that HTG-VLDL is a more potent stimulus to PAI-1 secretion than is NTG-VLDL. Experiments in which endothelial cells were exposed to VLDL subfractions indicated that large VLDL particles, in particular, induce PAI-1 release. Binding experiments demonstrated a specific cellular binding of both NTG- and HTG-VLDL to the cells, but HTG-VLDL bound about four times more effectively than NTG-VLDL. Exposure of the endothelial cells to an LDL receptor antibody was found to block 75% (p less than 0.005) of the VLDL-induced secretion of PAI-1 from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Hypertriglyceridemia / blood*
  • Lipoproteins, VLDL / metabolism
  • Lipoproteins, VLDL / pharmacology*
  • Male
  • Plasminogen Inactivators / metabolism*
  • Receptors, LDL / immunology
  • Receptors, LDL / metabolism
  • Umbilical Veins

Substances

  • Antibodies
  • Lipoproteins, VLDL
  • Plasminogen Inactivators
  • Receptors, LDL
  • VLDL receptor