title: Poly-L-histidine downregulates fibrinolysis.
abstract: The elevated level of histidine-rich glycoprotein was considered a risk factor of inherited thrombophilia. However, the mode of action remains largely unclear. In the current study, we employ poly-l-histidine (PLH) mimicking the histidine-rich region and determine whether PLH modulates urokinase (uPA)-dependent fibrinolysis. In an in vitro model, turbidity appearance and clearance monitored fibrin polymer formation and lysis, respectively. Fibrin polymer formed upon fibrinogen incubation with thrombin. In the presence of uPA or plasmin, fibrin polymer lysis took place in a dose-dependent manner as a function of time. We demonstrated that PLH significantly downregulated uPA-dependent fibrinolysis. PLH had no effect on plasminogen activation, as evidenced by no inhibitions on either uPA amidolytic activity or plasmin formation derived from its zymogen. Nor did PLH show any inhibition on plasmin amidolytic activity. PLH caused a profound delay of plasmin-dependent fibrinolysis upon pre-incubation of either plasmin or fibrinogen with PLH. The observations taken together suggest that the complex [plasmin-PLH-fibrin] formation significantly delayed plasmin-dependent fibrinolysis.
mesh_terms: D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006639:Histidine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D018716:Molecular Mimicry; D009391:Nephelometry and Turbidimetry; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology; D000099053:Histidine-Rich Glycoprotein
chemical_list: D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; C033223:polyhistidine; D006639:Histidine; D005337:Fibrin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator