Summary
Hemodynamic forces play a critical role in the pathogenesis of atherosclerosis as
evidenced by the focal nature of the disease. Oscillatory shear stress characterizes
the hemodynamic environment of plaque-prone areas as opposed to unidirectional shear
stress typical of plaque-free areas. These particular flow conditions modulate atherosclerosis-related
genes. Tissue factor (TF) initiates blood coagulation, contributes to vascular remodeling,
and is therefore a potential contributor in the development/progression of atherosclerosis.
We investigated the effect of oscillatory and unidirectional flows on TF using an
in vitro perfusion system. Human endothelial cells exposed for 24 h to oscillatory
shear stress, significantly increased TF mRNA, and TF protein expression (1.5-and
1.75-fold, respectively, p <0.01), and surface TF activity (twofolds-increase). Expression
of TF inhibitor (TFPI), mRNA and protein, remained unchanged as compared to static
conditions. Conversely, cells exposed to unidirectional shear, showed a decrease in
TF activity with a significant increase in TFPI mRNA and protein expression (1.5-and
1.8-fold, respectively, p <0.01). These results show for the first time that pulsatile
oscillatory shear stress induces a procoagulant phenotype of endothelial cells which
may favor formation/progression of atherothrombotic lesions.
Keywords
Tissue factor - tissue factor pathway inhibitor - shear stress - oscillatory flow
- atherosclerosis
