Wall Shear Stress (WSS) has been identified as an important factor in the pathogenesis of atherosclerosis. We developed a novel murine aortic coarctation model to alter the hemodynamic environment in vivo. The model utilizes the shape memory response of nitinol clips to provide a high degree of control over aortic diameter and subsequently WSS. We employed this model to test the hypothesis that acute changes in WSS in vivo induce upregulation of inflammatory proteins mediated by Reactive Oxygen Species (ROS). WSS was mapped through a computational fluid dynamic model and correlated to inflammatory marker expression. C57B16 control mice were compared to tempol treated, apocynin treated, p47phox KO, and catalase overexpressor mice in this study. The results show that the coarctation produces low mean oscillatory WSS in the region downstream of the clip. The WSS in this region correlates to a large increase in VCAM-1 expression in wild-type mice. This WSS dependent increase in protein expression is unchanged in animal models of decreased ROS. This suggests that although the redox state is important to the overall pathogenesis of the disease, individual ROS or ROS sources may not be sufficient to inhibit a WSS dependent inflammatory response. Further analysis with this model utilizing other reagent treatments, transgenic mice, and markers will allow us to analyze the functional contribution of transcription factors, ROS, and ROS sources to WSS dependent inflammatory protein expression.

This content is only available via PDF.
You do not currently have access to this content.