Decrease of fibrinolytic activity in human endothelial cells by arsenite.
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.
Jiang
Shinn-Jong
SJ
Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Lin
Tsun-Mei
TM
Wu
Hua-Lin
HL
Han
Huai-Song
HS
Shi
Guey-Yueh
GY
D018053:Arsenites / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008833:Microcirculation / Q000166:cytology; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000139:chemically induced / Q000209:etiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000187:drug effects; D018180:Thrombomodulin / Q000097:blood / Q000187:drug effects / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000187:drug effects / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology
D018053:Arsenites; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018180:Thrombomodulin; D010959:Tissue Plasminogen Activator; C015001:arsenite