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|Changes in the fibrinolytic components of cultured human umbilical vein endothelial cells induced by endotoxin, tumor necrosis factor-alpha and interleukin-1alpha|
|Authors: ||Orbe, J. (Josune)|
Chorda, C. (Carlos)
Montes, R. (Ramón)
Paramo, J.A. (José Antonio)
|Issue Date: ||1999|
|Publisher: ||Ferrata Storti Foundation|
|Publisher version: ||http://www.haematologica.org/content/84/4/306|
|Citation: ||Orbe J, Chorda C, Montes R, Paramo JA. Changes in the fibrinolytic components of cultured human umbilical vein endothelial cells induced by endotoxin, tumor necrosis factor-alpha and interleukin-1alpha. Haematologica 1999 Apr;84(4):306-311.|
BACKGROUND AND OBJECTIVE: Vascular fibrinolysis, a major natural defense mechanism against thrombosis, is a highly regulated process. The aim of this study was to evaluate the effect of endotoxin, tumor necrosis factor-alpha (TNFalpha) and interleukin-1alpha (IL-1alpha), on the fibrinolytic potential of cultured human umbilical vein endothelial cells (HUVEC).
DESIGN AND METHODS: Samples of stimulated conditioned media were collected over a period of 24 hours to determine: plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activity, PAI-1 mRNA, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen.
RESULTS: Similar changes were observed after endotoxin and cytokine stimulation: there was a significant increase of PAI activity (p<0.01), starting at 6 hours, which remained 24 hours after stimulation. PAI-1 mRNA also showed an important rise with these agents, although cytokines induced an earlier and more intense inhibitor response (up to 6-fold increase). PA activity increased significantly at 6 hours (p<0.01) to drop at 24 hours and was mainly related to the presence of u-PA.
INTERPRETATION AND CONCLUSIONS: We conclude that endotoxin,+TNFalpha and IL-1alpha induce profound alterations in the fibrinolytic potential of HUVEC, characterized by an initial rise of activators (u-PA) followed by a strong increase of PAI-1. These changes may be of pathophysiologic significance for thrombosis and inflammatory reactions.
|Permanent link: ||http://hdl.handle.net/10171/22267|
|Appears in Collections:||DA - CIMA - Cardiovasculares - Trombosis y Hemostasia - Artículos de Revista|
DA - CUN - Hematología y Hemoterapia - Artículos de revista
DA - CIMA - Cardiovasculares - Aterosclerosis e inflamación - Artículos de revista
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