High glucose impairs the endothelial shear stress response

Hemodynamic factors have been implicated in the development and progression of atherosclerotic vascular disease. In otherwise healthy individuals, atherosclerotic lesions localize at bifurcations and sharp curves in the vasculature. At these locations, laminar blood flow is interrupted and mean shear stress (SS) is low. An important clinical observation is that atherosclerotic plaque development in diabetic individuals does not follow this same pattern. Instead, diabetic vasculature has a diffuse pattern where lesions spread into regions of greater SS. This considerable difference in plaque distribution between non-diabetic and diabetic subjects leads to the hypothesis that diabetic endothelial cells fail to properly sense or respond to fluid SS.;An in vitro model of diabetes was used to assess the effects of high glucose concentrations on components of aortic endothelial cells that are involved in the cellular SS response. Experimental results indicate that endothelial cells cultured in high glucose exhibit an impaired response to fluid SS that appears to be caused by a decreased sensitivity to mechanical forces. Investigation into the effects of high glucose on both the endothelial mechanosensing (via the heparan sulfate proteoglycan) and the mechanoresponse mechanisms (via integrin and cytoskeletal expression) reveal two sources of glucose modifications. The consequence of these changes is an impaired cellular response to shear stress. These findings may contribute to an understanding of diffuse diabetic vascular disease.