[Effect of shear stress on hemostatic regulation in endothelium].
The vascular endothelium plays a pivotal role in regulating the hemostatic system. Various cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to perturb endothelial cells to reduce antithrombogenicity. On the other hand, blood flow has been shown to affect the endothelium to maintain its antithrombogenicity under some levels of shear stress in the laminar flow system. We examined the role of hemodynamic forces on the vascular system under cytokine stimulation using a cone-plate type viscometer. Treatment of endothelial cells with either IL-1 beta or TNF-alpha under static conditions increased PAI-1, vWF and prostacyclin release, while t-PA secretion was unchanged. When cells were exposed to steady shear stress of 0, 6, 12, 18 and 24 dyne/cm2, the release of t-PA, t-PA-PAI complex and prostacyclin elevated with the increase of shear stress intensity, while a gradual decrease of total PAI-1 secretion was observed and vWF secretion was unchanged. On the contrary, active PAI-1 secretion was significantly decreased under the shear stress of over 18 dyne/cm2. Interestingly, cytokines, which did not affect t-PA secretion of resting cells, increased the t-PA secretion and had an additive effect on prostacyclin secretion with shear stress under the shear stress of over 18 dyne/cm2. PAI-1 elevation induced by cytokines was markedly abolished under the same shear forces. No additive effect was observed in the secretion of vWF. Thus, shear stress attenuates the alteration of the balance in the fibrinolytic and coagulation system induced by cytokines. These findings clearly indicate that hemodynamic forces play a crucial role in regulating the hemostatic activity in vivo.
Kawai
Y
Y
Department of Laboratory Medicine, Keio University, School of Medicine, Tokyo.
Matsumoto
Y
Y
Ikeda
Y
Y
Yamamoto
H
H
Satoh
K
K
Watanabe
K
K
D001777:Blood Coagulation; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006487:Hemostasis; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013314:Stress, Mechanical; D013927:Thrombosis / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator