Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells.

Abstract

Decreased fibrinolytic activity has been reported in atherosclerotic cardiovascular diseases. To determine whether oxidized low-density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids, and levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) antigens in the conditioned medium were measured by enzyme-linked immunosorbent assay. Ox-LDL (30 micrograms protein/mL) and its extracted lipid (50 micrograms cholesterol/mL) stimulated PAI-1 release by 42 +/- 3% and 29 +/- 3% of control cultures, respectively, whereas Ox-LDL and its lipid inhibited t-PA release by 42 +/- 4% and 53 +/- 3% of control cultures, respectively. Native LDL and its lipid were inactive on their release. Ox-LDL depleted of hydrophilic lipids, which was prepared by the incubation with defatted albumin (an acceptor for hydrophilic...