Research Article| Volume 217, ISSUE 2, P135-141, February 15, 2004

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

  • Jeong Ai Kim
    Corresponding author. Tel.: +1-714-456-6808; fax: +1-714-456-6894.
    Department of Neurology, University of California, Irvine, College of Medicine, 101 The City Drive South, Building. 55, Rm. 121, Orange, CA 92868-5120, USA
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  • Nam D. Tran
    Department of Neurology, University of California, Irvine, College of Medicine, 101 The City Drive South, Building. 55, Rm. 121, Orange, CA 92868-5120, USA
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  • Judith A. Berliner
    Department of Pathology and Medicine, University of California, Los Angeles, Los Angeles, CA, USA
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  • Mark J. Fisher
    Department of Neurology, University of California, Irvine, College of Medicine, 101 The City Drive South, Building. 55, Rm. 121, Orange, CA 92868-5120, USA

    Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA
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      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.


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