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 f or 16-18 hours in medium 199 with or without different concentrations of LDL and acetyl-LDL and PAI-I antigen levels were measured in condit ioned medium. LDL and acetyl-LDL increased die release of PAI-1 by EC in a concentration-dependent manner. The effect was specific for PAI-I because tissue type plasminogen activator (t-PA) and expression of pr ocoagulant activity were not affected by either lipoprotein. The obser vation that native and acetyl-LDL, which are known to interact with di fferent receptors on EC, exert the same stimulatory effect on PAI-1 re lease rules out the possibility of an involvement of the LDL receptor in mediating this effect. Experiments carried out incubating native LD L in the presence of a monoclonal antibody against LDL receptor and us ing binding-defective LDL with a reduced affinity for the LDL receptor (approximately 50% with respect to normal LDL) further excluded an in volvement of the classical LDL receptor in mediating the effect of the lipoproteins on PAI-1 synthesis by EC.