Influence of TNF-alpha and biomechanical stress on endothelial anti- and prothrombotic genes.
Biomechanical stress modulates vascular tone, vascular remodelling and the spatial localisation of atherosclerotic plaques. Inflammatory cytokines, such as TNF-alpha, regulate expression of genes that impair the function of endothelial cells. This study investigates the combinatory effect of different biomechanical stresses and TNF-alpha on the expression of endothelial anti- and prothrombotic genes. Human umbilical vein endothelial cells were exposed to TNF-alpha and different levels of static/pulsatile tensile stress or shear stress. The response in endothelial cells to TNF-alpha was not modulated by tensile stress. However, shear stress was a more potent stimulus. Shear stress counteracted the cytokine-induced expression of VCAM-1, and the cytokine-suppressed expression of thrombomodulin and eNOS. Shear stress and TNF-alpha additively induced PAI-1, whereas shear stress blocked the cytokine effect on t-PA and u-PA. A flow profile characterized by high laminar shear stress seems to render the endothelial cell more resistant to inflammatory stress.
Bergh
N
N
Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Ulfhammer
E
E
Glise
K
K
Jern
S
S
Karlsson
L
L
D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D033081:Shear Strength; D013314:Stress, Mechanical; D013718:Tensile Strength; D013927:Thrombosis / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator