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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.
Haematologica 1999; 84(4):306-11H

Abstract

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.

Authors+Show Affiliations

Laboratory of Vascular Biology and Thrombosis, Hematology Service, School of Medicine, University of Navarra, Pamplona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10190943

Citation

Orbe, J, et al. "Changes in the Fibrinolytic Components of Cultured Human Umbilical Vein Endothelial Cells Induced By Endotoxin, Tumor Necrosis Factor-alpha and Interleukin-1alpha." Haematologica, vol. 84, no. 4, 1999, pp. 306-11.
Orbe J, Chordá C, Montes R, et al. Changes in the fibrinolytic components of cultured human umbilical vein endothelial cells induced by endotoxin, tumor necrosis factor-alpha and interleukin-1alpha. Haematologica. 1999;84(4):306-11.
Orbe, J., Chordá, C., Montes, R., & Páramo, J. A. (1999). Changes in the fibrinolytic components of cultured human umbilical vein endothelial cells induced by endotoxin, tumor necrosis factor-alpha and interleukin-1alpha. Haematologica, 84(4), pp. 306-11.
Orbe J, et al. Changes in the Fibrinolytic Components of Cultured Human Umbilical Vein Endothelial Cells Induced By Endotoxin, Tumor Necrosis Factor-alpha and Interleukin-1alpha. Haematologica. 1999;84(4):306-11. PubMed PMID: 10190943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in the fibrinolytic components of cultured human umbilical vein endothelial cells induced by endotoxin, tumor necrosis factor-alpha and interleukin-1alpha. AU - Orbe,J, AU - Chordá,C, AU - Montes,R, AU - Páramo,J A, PY - 1999/4/6/pubmed PY - 1999/4/6/medline PY - 1999/4/6/entrez SP - 306 EP - 11 JF - Haematologica JO - Haematologica VL - 84 IS - 4 N2 - 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. SN - 0390-6078 UR - https://www.unboundmedicine.com/medline/citation/10190943/Changes_in_the_fibrinolytic_components_of_cultured_human_umbilical_vein_endothelial_cells_induced_by_endotoxin_tumor_necrosis_factor_alpha_and_interleukin_1alpha_ L2 - http://www.haematologica.org/cgi/pmidlookup?view=long&amp;pmid=10190943 DB - PRIME DP - Unbound Medicine ER -