Tissue factor activity is upregulated in human endothelial cells exposed to oscillatory shear stress.
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 pro-coagulant phenotype of endothelial cells which may favor formation/progression of atherothrombotic lesions.
Mazzolai
Lucia
L
Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland. Lucia.Mazzolai@chuv.hospvd.ch
Silacci
Paolo
P
Bouzourene
Karima
K
Daniel
François
F
Brunner
Hans
H
Hayoz
Daniel
D
D017209:Apoptosis / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism*; D004867:Equipment Design; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008955:Models, Cardiovascular; D010477:Perfusion; D010507:Periodicity; D013314:Stress, Mechanical; D013925:Thromboplastin / Q000378:metabolism*; D015854:Up-Regulation
D013925:Thromboplastin