Upregulation of Dickkopf1 by oscillatory shear stress accelerates atherogenesis

Numerous clinical studies have highlighted the pivotal role dickkopf (dkk) 1 plays in atherosclerosis, but the underlying mechanisms remain unknown. the present study was designed to explore the contribution of dkk1 to the development of atherosclerosis under oscillatory shear stress. oscillatory shear stress applied to endothelial cells induced dkk1 expression, which peaked at 6 h. sirna knockdown or silencing dkk1 by lentiviral gene delivery counteracted the increased monocyte adhesion and impaired endothelial tight junction induced by oscillatory shear stress, thereby attenuating atherogenesis in apoe−/− mice. as well, activation of endothelial proteinase-activated receptor 1 (par1) and its downstream transcription factor, camp response element-binding protein (creb), was critical to the increased expression of dkk1 under oscillatory shear stress. we provide evidence that dkk1 contributes to the development of atherosclerosis under conditions of oscillatory shear stress. a better understanding of the role played by dkk1 in atherogenesis provide clinicians with opportunities to prevent atherosclerosis.