Antithrombotic regulation in human endothelial cells by fibrinolytic factors.
Vascular endothelial cells (ECs) modulate the blood fibrinolytic system by secreting tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and their inhibitor, type-1 plasminogen activator inhibitor (PAI-1). ECs also express t-PA receptors (t-PAR) and u-PA receptors (u-PAR) on their cell surfaces, assembling both enzymes to regulate the cellular fibrinolytic activity. In addition, ECs modulate these factors in response to several stimuli. Fibrin clots on ECs induce the up- and downregulation of t-PA and PAI-1 production, respectively, thus causing an effective lysis of the fibrin clot. Heat shock (43 degrees C) increases the expression of u-PA, t-PA, PAI-1, and u-PAR by which ECs become more fibrinolytic around the cells. Furthermore, because ECs possess t-PAR and u-PAR on their cell surfaces, the binding of t-PA and u-PA is a critical event, which affords ECs the localized and condensed fibrinolytic potential. Therefore, ECs play a central role in antithrombotic activity by regulating the levels of these fibrinolytic factors.
Fukao
H
H
Department of Physiology, Kinki University School of Medicine, Osakasayama City, Japan. fukao@med.kindai.ac.jp
Matsuo
O
O
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D019898:Autocrine Communication; D001777:Blood Coagulation; D015152:Blotting, Northern; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005337:Fibrin / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005576:Colforsin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005337:Fibrin; D000242:Cyclic AMP; D011493:Protein Kinase C; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate