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Hemodynamic forces modulate the effects of cytokines on fibrinolytic activity of endothelial cells.
Blood 1996; 87(6):2314-21Blood

Abstract

We investigated the effects of hemodynamic force on fibrinolytic activity of cultured human umbilical vein endothelial cells stimulated by cytokines, using a modified cone-plate viscometer in which well-controlled and -defined shear forces were generated. Treatment of the cells with interleukin (IL)-beta or tumor necrosis factor alpha (TNFalpha) under static conditions had no effect on tissue plasminogen activator (t-PA) secretion, while release of plasminogen activator inhibitor 1 (PAI-1) increased. When cells were exposed to increasing shear stress up to 24 dynes/cm2, levels of t-PA and t-PA/PAI-1 complex significantly increased relative to shear stress, while total PAI-1 and active PAI-1 secretion decreased gradually. In the presence of IL-1beta or TNFalpha, the increase in production of t-PA and the t-PA/PAI-1 complex was further augmented. Dot blot hybridization analysis of cultured cells in similar experimental conditions using t-PA and PAI-1 cDNA probes revealed no t-PA mRNA in 3 microg total RNA from static endothelial cells under resting or cytokine-stimulated conditions, but abundant t-PA mRNA was detected in cells subjected to a shear force of 18 dynes/cm2, and the increase was further augmented by addition of cytokines. In contrast, PAI-1 mRNA was detected in resting and cytokine-stimulated, nonsheared endothelial cells, but levels decreased after exposure to shear stress, even in the presence of cytokines. These results indicate a role for hemodynamic forces in regulating fibrinolytic activity with or without cytokine stimulation.

Authors+Show Affiliations

Departments of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

8630393

Citation

Kawai, Y, et al. "Hemodynamic Forces Modulate the Effects of Cytokines On Fibrinolytic Activity of Endothelial Cells." Blood, vol. 87, no. 6, 1996, pp. 2314-21.
Kawai Y, Matsumoto Y, Watanabe K, et al. Hemodynamic forces modulate the effects of cytokines on fibrinolytic activity of endothelial cells. Blood. 1996;87(6):2314-21.
Kawai, Y., Matsumoto, Y., Watanabe, K., Yamamoto, H., Satoh, K., Murata, M., ... Ikeda, Y. (1996). Hemodynamic forces modulate the effects of cytokines on fibrinolytic activity of endothelial cells. Blood, 87(6), pp. 2314-21.
Kawai Y, et al. Hemodynamic Forces Modulate the Effects of Cytokines On Fibrinolytic Activity of Endothelial Cells. Blood. 1996 Mar 15;87(6):2314-21. PubMed PMID: 8630393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemodynamic forces modulate the effects of cytokines on fibrinolytic activity of endothelial cells. AU - Kawai,Y, AU - Matsumoto,Y, AU - Watanabe,K, AU - Yamamoto,H, AU - Satoh,K, AU - Murata,M, AU - Handa,M, AU - Ikeda,Y, PY - 1996/3/15/pubmed PY - 1996/3/15/medline PY - 1996/3/15/entrez SP - 2314 EP - 21 JF - Blood JO - Blood VL - 87 IS - 6 N2 - We investigated the effects of hemodynamic force on fibrinolytic activity of cultured human umbilical vein endothelial cells stimulated by cytokines, using a modified cone-plate viscometer in which well-controlled and -defined shear forces were generated. Treatment of the cells with interleukin (IL)-beta or tumor necrosis factor alpha (TNFalpha) under static conditions had no effect on tissue plasminogen activator (t-PA) secretion, while release of plasminogen activator inhibitor 1 (PAI-1) increased. When cells were exposed to increasing shear stress up to 24 dynes/cm2, levels of t-PA and t-PA/PAI-1 complex significantly increased relative to shear stress, while total PAI-1 and active PAI-1 secretion decreased gradually. In the presence of IL-1beta or TNFalpha, the increase in production of t-PA and the t-PA/PAI-1 complex was further augmented. Dot blot hybridization analysis of cultured cells in similar experimental conditions using t-PA and PAI-1 cDNA probes revealed no t-PA mRNA in 3 microg total RNA from static endothelial cells under resting or cytokine-stimulated conditions, but abundant t-PA mRNA was detected in cells subjected to a shear force of 18 dynes/cm2, and the increase was further augmented by addition of cytokines. In contrast, PAI-1 mRNA was detected in resting and cytokine-stimulated, nonsheared endothelial cells, but levels decreased after exposure to shear stress, even in the presence of cytokines. These results indicate a role for hemodynamic forces in regulating fibrinolytic activity with or without cytokine stimulation. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/8630393/Hemodynamic_forces_modulate_the_effects_of_cytokines_on_fibrinolytic_activity_of_endothelial_cells_ DB - PRIME DP - Unbound Medicine ER -