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Related Experiment Videos

Decrease of fibrinolytic activity in human endothelial cells by arsenite.

Shinn-Jong Jiang1, Tsun-Mei Lin, Hua-Lin Wu

  • 1Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

Thrombosis Research
|February 28, 2002
PubMed
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Arsenite in drinking water may cause Blackfoot disease by reducing blood clot breakdown. This study found arsenite significantly impairs fibrinolytic activity in microvascular endothelial cells, potentially explaining the disease mechanism.

Area of Science:

  • Vascular Biology
  • Environmental Toxicology
  • Biochemistry

Background:

  • Blackfoot disease (BFD) is an endemic peripheral vascular occlusive disease linked to arsenic in drinking water.
  • BFD patients exhibit lower tissue-type plasminogen activator (t-PA) and higher plasminogen activator inhibitor, Type 1 (PAI-1) levels.

Purpose of the Study:

  • To investigate the effects of arsenite on fibrinolytic and anticoagulant activities in cultured endothelial cells.
  • To determine if arsenite impacts macrovascular and microvascular endothelial cell function.

Main Methods:

  • Cultured human microvascular endothelial cells (HMEC-1) and human umbilical vein endothelial cells (HUVECs) were incubated with arsenite.
  • Messenger RNA (mRNA) levels for t-PA, PAI-1, and thrombomodulin (TM) were analyzed.

Related Experiment Videos

  • PAI activity and TM antigen levels were quantified.

    • Main Results:

    • Arsenite decreased t-PA mRNA and increased PAI-1 mRNA and PAI activity specifically in HMEC-1 cells.
    • Arsenite inhibited thrombomodulin (TM) mRNA expression and reduced TM antigen levels in HMEC-1.
    • HUVECs showed less significant responses to arsenite compared to HMEC-1.

    Conclusions:

    • Arsenite exerts a more pronounced effect on microvascular endothelial cells (HMEC-1) than macrovascular cells (HUVECs).
    • Arsenite-induced reduction in fibrinolytic activity and TM expression in HMEC-1 may contribute to the pathogenesis of Blackfoot disease.