Effect of atherogenic lipoproteins on PAI-1 synthesis by endothelial cells.
Cultured human umbilical vein endothelial cells (EC) exposed to native and acetylated low density lipoproteins (LDL and acetyl-LDL) show an increased synthesis of PAI-1. Confluent EC monolayers were incubated for 16-18 hours in medium 199 with or without different concentrations of LDL and acetyl-LDL and PAI-1 antigen levels were measured in conditioned medium. LDL and acetyl-LDL increased the release of PAI-1 by EC in a concentration-dependent manner. The effect was specific for PAI-1 because tissue type plasminogen activator (t-PA) and expression of procoagulant activity were not affected by either lipoprotein. The observation that native and acetyl-LDL, which are known to interact with different receptors on EC, exert the same stimulatory effect on PAI-1 release rules out the possibility of an involvement of the LDL receptor in mediating this effect. Experiments carried out incubating native LDL in the presence of a monoclonal antibody against LDL receptor and using binding-defective LDL with a reduced affinity for the LDL receptor (approximately 50% with respect to normal LDL) further excluded an involvement of the classical LDL receptor in mediating the effect of the lipoproteins on PAI-1 synthesis by EC.
Camera
M
M
Institute of Pharmacological Sciences, University of Milan, Italy.
Mussoni
L
L
Maderna
P
P
Sironi
L
L
Prati
L
L
Colli
S
S
Bernini
F
F
Corsini
A
A
Tremoli
E
E
D001161:Arteriosclerosis / Q000209:etiology; D001709:Biotechnology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D011973:Receptors, LDL / Q000378:metabolism
D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D011973:Receptors, LDL; C032629:acetyl-LDL