TISSUE FACTOR EXPRESSION IS DIFFERENTIALLY MODULATED BY CYCLIC MECHANICAL STRAIN IN VARIOUS HUMAN ENDOTHELIAL-CELLS

Many of the hemostatic properties of endothelium are modulated by chem ical and mechanical stimuli The nature of such endothelial cell (EC) r esponses often depends upon the anatomical origin of the cells within the vascular tree. In the present study, we used a chromogenic assay t o investigate the effect of cyclic strain or tumor necrosis factor alp ha (TNF alpha), or both, on tissue factor (TF) activity in human EC de rived from umbilical veins (HUVEC), aortae (HAEC), and derma microvess els (HMVEC). Basal TF activities were low in all three cell types. Inc ubation for 5 h with (10 ng/ml) TNF alpha resulted in quantitatively d iverse elevation of TF activity in all three EC types. Exposure to cyc lic strain for 5 h induced significant elevation of TF activity only i n HMVEC and HAEC. Concomitant application of cyclic strain and TNF alp ha resulted in synergistic elevation of TF expression only in HMVEC. P harmacologic elevation of cyclic AMP (cAMP) levels and inhibition of p rotein kinase C (PKC) levels inhibited TNF alpha-induced TF expression in all EC types. However, none of these treatments affected the stimu latory action of cyclic strain in HMVEC. Thus, we have shown that TNF alpha differentially increases TF activity in human EC of various orig ins, that cyclic strain variably modulates TF activity in human EC, an d that both PKC and cAMP mediate TNF alpha-induced TF activity, wherea s cyclic strain acts independently of these pathways. These results sh ow differential modulation of the procoagulant potential of diverse hu man endothelial cells in vitro by hemodynamic stimuli.