Influence of TNF-alpha and biomechanical stress on endothelial anti- and prothrombotic genes

Biochem Biophys Res Commun. 2009 Jul 31;385(3):314-8. doi: 10.1016/j.bbrc.2009.05.046. Epub 2009 May 18.

Abstract

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.

MeSH terms

  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Plasminogen Activator Inhibitor 1 / genetics
  • Shear Strength
  • Stress, Mechanical*
  • Tensile Strength
  • Thrombosis / genetics*
  • Tissue Plasminogen Activator / genetics
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*
  • Urokinase-Type Plasminogen Activator / genetics

Substances

  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Tumor Necrosis Factor-alpha
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator