Regulation of tissue factor expression in human microvascular endothelial cells by nitric oxide.
Regulation of tissue factor expression in human microvascular endothelial cells by nitric oxide.
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DOI：
10.1161/01.cir.101.18.2144
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发表时间：
2000-05
期刊：
影响因子：
37.8
通讯作者：
Yinke Yang;J. Loscalzo
中科院分区：
文献类型：
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作者：
Yinke Yang;J. Loscalzo
组织因子（TF）是正常止血和动脉粥样硬化血栓形成疾病中凝血酶生成的关键决定因素。一氧化氮在血管系统中具有抗血栓形成和抗动脉粥样硬化作用，但其在TF表达调节中的作用尚未研究。方法和结果为了研究内源性内皮源性一氧化氮对TF表达和活性的影响，我们用脂多糖或白细胞介素-1 β诱导人微血管内皮细胞中的TF，并通过北方和Western印迹观察到TF活性和表达的剂量和时间依赖性增加。L-精氨酸，一氧化氮合酶的主要底物，加入到培养基中，在24小时显著抑制TF活性的诱导（脂多糖诱导66%，白细胞介素-1 β诱导59%）。这些活动的变化伴随着TF蛋白和稳态mRNA的相关变化。D-精氨酸没有影响，内源性一氧化氮的产生抑制未能增加TF的表达。结论：这些数据表明，增强生产的内皮源性一氧化氮减少内毒素和精氨酸诱导的表达TF，从而，血栓形成前的内皮细胞表型。
BACKGROUND Tissue factor (TF) is a critical determinant of thrombin generation in normal hemostasis and in atherothrombotic disease. Nitric oxide has both antithrombotic and antiatherosclerotic actions in the vasculature, yet its role in the regulation of TF expression has not been examined. METHODS AND RESULTS To study the effect of endogenous endothelium-derived nitric oxide on TF expression and activity, we induced TF in human microvascular endothelial cells with lipopolysaccharide or interleukin-1beta and observed a dose- and time-dependent increase in TF activity and expression by Northern and Western blotting. L-Arginine, the principal substrate for nitric oxide synthases, added to the media suppressed the induction of TF activity significantly (by 66% for lipopolysaccharide induction and by 59% for interleukin-1beta induction) at 24 hours. These changes in activity were accompanied by correlative changes in TF protein and steady-state mRNA. D-Arginine had no effect, and inhibition of endogenous nitric oxide production failed to increase TF expression. CONCLUSIONS These data suggest that enhanced production of endothelium-derived nitric oxide reduces endotoxin- and cytokine-induced expression of TF and, thereby, the prothrombotic phenotype of the endothelial cell.