Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells

Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary endothelial cells (BEC) incubated with MM-LDL (25 mug/ml) for 24 It showed increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels increased two-fold (16.8 +/-7.6 vs. 7.6 +/- 2.1 ng/ml, p < 0.05), whereas tPA protein levels decreased by 45% (1.3 +/- 0.5 ng/ml vs. 2.3 +/- 0.7 ng/ml, p < 0.05), and TM protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity was increased 35% (18.4 +/- 5.0 vs. 24.8 +/- 5.2 AU/ml, p < 0.05), while TM activity was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on brain capillary endothelial cells, reducing both endothelial fibrinolytic capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function (downregulating TM). These results suggest that MM-LDL may contribute to thrombus formation in the brain. (C) 2003 Elsevier B.V. All rights reserved.