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Updated: Feb 7, 2026

Stimulation of Vascular Endothelial Cells Using Neutrophil Extracellular Traps in the Presence of Low-Density Lipoprotein
Published on: August 12, 2025
Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells
Jeong Ai Kim1, Nam D Tran, Judith A Berliner
1Department of Neurology, University of California, Irvine, College of Medicine, 101 The City Drive South, Building. 55, Rm. 121, Orange, CA 92868-5120, USA. jkim8@uci.edu
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 microg/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.
Insights
Minimally oxidized LDL (MM-LDL) promotes blood clot formation in the brain. MM-LDL reduces anticoagulant and clot-dissolving factors in brain endothelial cells, increasing thrombus risk.
Area of Science:
- Cardiovascular Biology
- Neuroscience
- Thrombosis Research
Background:
- Minimally oxidized low-density lipoprotein (MM-LDL) is recognized as a significant atherogenic factor.
- Brain capillary endothelial cells play a crucial role in regulating cerebral blood flow and hemostasis.
Purpose of the Study:
- To investigate the impact of MM-LDL on the expression and activity of key hemostatic factors in brain capillary endothelial cells.
- To determine the pro-thrombotic potential of MM-LDL in the cerebral vasculature.
Main Methods:
- Cultured bovine brain capillary endothelial cells (BEC) were exposed to MM-LDL (25 microg/ml) for 24 hours.
- Quantitative analysis of mRNA and protein levels for PAI-1, tPA, and TM was performed.
- Functional assays measured PAI-1 and TM activity.
Main Results:
- MM-LDL significantly upregulated PAI-1 mRNA (approx. 7-fold) and protein (2-fold) levels.
- MM-LDL markedly downregulated tPA mRNA (84%) and protein (45%) levels.
- MM-LDL decreased TM mRNA (75%) and protein (40%) levels, along with reduced TM activity (30%).
- PAI-1 activity increased by 35% following MM-LDL exposure.
Conclusions:
- MM-LDL exerts pro-thrombotic effects on brain capillary endothelial cells.
- MM-LDL impairs the brain's fibrinolytic capacity by downregulating tPA and upregulating PAI-1.
- MM-LDL reduces anticoagulant function by downregulating TM, suggesting a role in cerebral thrombus formation.
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