title: Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells.
abstract: Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary endothelial cells (BEC) incubated with MM-LDL (25 microg/ml) for 24 h showed increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels increased two-fold (16.8+/-7.6 vs. 7.6+/-2.1 ng/ml, p<0.05), whereas tPA protein levels decreased by 45% (1.3+/-0.5 ng/ml vs. 2.3+/-0.7 ng/ml, p<0.05), and TM protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity was increased 35% (18.4+/-5.0 vs. 24.8+/-5.2 AU/ml, p<0.05), while TM activity was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on brain capillary endothelial cells, reducing both endothelial fibrinolytic capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function (downregulating TM). These results suggest that MM-LDL may contribute to thrombus formation in the brain.
authors.affiliation: Department of Neurology, University of California, Irvine, College of Medicine, 101 The City Drive South, Building. 55, Rm. 121, Orange, CA 92868-5120, USA. jkim8@uci.edu
authors.forename: Jeong Ai
authors.initials: JA
authors.lastname: Kim
authors.forename: Nam D
authors.initials: ND
authors.lastname: Tran
authors.forename: Judith A
authors.initials: JA
authors.lastname: Berliner
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D020767:Intracranial Thrombosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D001779:Blood Coagulation Factors; D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018180:Thrombomodulin; C099252:oxidized low density lipoprotein; D010959:Tissue Plasminogen Activator