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Silverman M. D.; Manolopoulos, V. G.; Unsworth, B. R.; Lelkes, P. I.
Blood Coagulation & Fibrinolysis: April 1996
Research Paper: PDF Only

Many of the hemostatic properties of endothelium are modulated by chemical and mechanical stimuli. The nature of such endothelial cell (EC) responses often depends upon the anatomical origin of the cells within the vascular tree. In the present study, we used a chromogenic assay to investigate the effect of cyclic strain or tumor necrosis factor alpha (TNFα), or both, on tissue factor (TF) activity in human EC derived from umbilical veins (HUVEC), aortae (HAEC), and dermal microvessels (HMVEC). Basal TF activities were low in all three cell types. Incubation for 5 h with (10 ng/ml) TNFα resulted in quantitatively diverse elevation of TF activity in all three EC types. Exposure to cyclic strain for 5 h induced significant elevation of TF activity only in HMVEC and HAEC. Concomitant application of cyclic strain and TNFα resulted in synergistic elevation of TF expression only in HMVEC. Pharmacologic elevation of cyclic AMP (cAMP) levels and inhibition of protein kinase C (PKC) levels inhibited TNFα-induced TF expression in all EC types. However, none of these treatments affected the stimulatory action of cyclic strain in HMVEC. Thus, we have shown that TNFα differentially increases TF activity in human EC of various origins, that cyclic strain variably modulates TF activity in human EC, and that both PKC and cAMP mediate TNFα-induced TF activity, whereas cyclic strain acts independently of these pathways. These results show differential modulation of the procoagulant potential of diverse human endothelial cells in vitro by hemodynamic stimuli.

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