title: Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein.
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)
authors: King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
authors: A
authors: A
authors: Stiko-Rahm
authors: B
authors: B
authors: Wiman
authors: A
authors: A
authors: Hamsten
authors: J
authors: J
authors: Nilsson
mesh_terms: D000906:Antibodies; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011973:Receptors, LDL / Q000276:immunology / Q000378:metabolism; D014471:Umbilical Veins
chemical_list: D000906:Antibodies; D008079:Lipoproteins, VLDL; D015849:Plasminogen Inactivators; D011973:Receptors, LDL; C036053:VLDL receptor