Jiang Shinn-Jong, Lin Tsun-Mei, Wu Hua-Lin, Han Huai-Song, Shi Guey-Yueh
Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Thromb Res. 2002 Jan 1;105(1):55-62. doi: 10.1016/s0049-3848(01)00397-8.
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 1 (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-1 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.
乌脚病（BFD）是一种发生在台湾西南海岸的地方性周围血管闭塞性疾病。据信，自流水井饮用水中的砷在该疾病的发展中起重要作用。我们之前已经表明，乌脚病患者的组织型纤溶酶原激活物（t-PA）抗原水平显著低于正常对照组，而纤溶酶原激活物抑制剂1型（PAI-1）抗原水平则高于正常对照组。本研究的目的是探讨亚砷酸盐对培养的大血管和微血管内皮细胞纤溶和抗凝活性的影响。用亚砷酸盐处理人微血管内皮细胞（HMEC-1），而不是人脐静脉内皮细胞（HUVECs），会导致t-PA mRNA水平降低，PAI-1 mRNA水平和PAI活性升高。亚砷酸盐还可抑制HMEC-1中血栓调节蛋白（TM）mRNA的表达并降低TM抗原水平。总之，与HUVECs相比，亚砷酸盐对HMEC-1降低纤溶活性的影响更大，可能是导致与乌脚病相关的纤溶能力降低的原因。
