title: Effect of atherogenic lipoproteins on PAI-1 synthesis by endothelial cells.
abstract: 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.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Camera
authors.forename: L
authors.initials: L
authors.lastname: Mussoni
authors.forename: P
authors.initials: P
authors.lastname: Maderna
authors.forename: L
authors.initials: L
authors.lastname: Sironi
authors.forename: L
authors.initials: L
authors.lastname: Prati
authors.forename: S
authors.initials: S
authors.lastname: Colli
authors.forename: F
authors.initials: F
authors.lastname: Bernini
authors.forename: A
authors.initials: A
authors.lastname: Corsini
authors.forename: E
authors.initials: E
authors.lastname: Tremoli
mesh_terms: 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
chemical_list: D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D011973:Receptors, LDL; C032629:acetyl-LDL