title: Decrease of fibrinolytic activity in human endothelial cells by arsenite.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Shinn-Jong
authors.initials: SJ
authors.lastname: Jiang
authors.forename: Tsun-Mei
authors.initials: TM
authors.lastname: Lin
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Huai-Song
authors.initials: HS
authors.lastname: Han
authors.forename: Guey-Yueh
authors.initials: GY
authors.lastname: Shi
mesh_terms: 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
chemical_list: D018053:Arsenites; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018180:Thrombomodulin; D010959:Tissue Plasminogen Activator; C015001:arsenite