Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein.
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)
Stiko-Rahm
A
A
King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
Wiman
B
B
Hamsten
A
A
Nilsson
J
J
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
D000906:Antibodies; D008079:Lipoproteins, VLDL; D015849:Plasminogen Inactivators; D011973:Receptors, LDL; C036053:VLDL receptor