Decrease of fibrinolytic activity in human endothelial cells by arsenite
Decrease of fibrinolytic activity in human endothelial cells by arsenite
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DOI：
10.1016/s0049-3848(01)00397-8
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发表时间：
2002-01-01
影响因子：
7.5
通讯作者：
Shi, GY
中科院分区：
文献类型：
--
作者：
Jiang, SJ;Lin, TM;Shi, GY
黑脚病是一种发生于台湾西南海岸的地方性周围血管闭塞性疾病。认为自流威尔斯井饮用水中的砷在该病的发生发展中起重要作用。我们以前已经表明，BFD患者有显着较低的组织型纤溶酶原激活物（t-PA）抗原水平和较高的纤溶酶原激活物抑制剂，I型（派-1）抗原水平比正常对照组。本研究旨在探讨亚砷酸盐对体外培养的大血管和微血管内皮细胞纤溶和抗凝活性的影响。培养的人微血管内皮细胞（HMEC-1）与亚砷酸盐孵育后，t-PA mRNA水平下降，PAI-Ⅰ mRNA水平和派活性均升高，而人脐静脉内皮细胞（HUVECs）与亚砷酸盐孵育后无明显变化。亚砷酸钠还可抑制HMEC-1血栓调节蛋白（TM）mRNA表达，降低TM抗原水平。总之，与HUVEC相比，亚砷酸盐在降低纤溶活性方面对HMEC-1具有更大的影响，并且可能是与BFD相关的纤溶能力降低的原因。(C)2002爱思唯尔科技有限公司版权所有。
Blackfoot disease (BFD) is an endemic peripheral vascular occlusive disease that occurred in the southwest coast of Taiwan. It is believed that arsenic in the drinking water from artesian wells plays an important role in the development of the disease. We have previously shown that BFD patients had significant lower tissue-type plasminogen activator (t-PA) antigen level and higher plasminogen activator inhibitor, Type I (PAI-1) antigen level than normal controls. The purpose of this study was to investigate the effects of arsenite on the fibrinolytic and anticoagulant activities of cultured macrovascular and microvascular endothelial cells. Incubation of human microvascular endothelial cells (HMEC-1), but not human umbilical vein endothelial cells (HUVECs), with arsenite caused a decrease of t-PA mRNA level, a rise of both PAI-I mRNA level and PAI activity. Arsenite could also inhibit the thrombomodulin (TM) mRNA expression and reduce the TM antigen level in HMEC-1. In conclusion, arsenite had a greater effect on HMEC-1 as compared to HUVECs in lowering the fibrinolytic activity and may be responsible for the reduced capacity of Fibrinolysis associated with BFD. (C) 2002 Elsevier Science Ltd. All rights reserved.