Abstract
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 μg/ml) for 24 h 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.
Keywords
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Article info
Publication history
Accepted:
September 10,
2003
Received in revised form:
August 25,
2003
Received:
October 15,
2002
Identification
Copyright
© 2003 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
