Sudden onset of flow creates significant temporal shear stress gradients that stimulate endothelial cell proliferation, providing insights into atherosclerotic plaque generation.
May implicate temporal shear gradients in endothelial proliferation underlying atherosclerosis; extends in vitro models but leaves in vivo relevance open.
Endothelial cells in blood vessels are exposed to bloodflow and thus fluid shear stress. In arterial bifurcations and stenoses, disturbed flow causes zones of recirculation and stagnation, which are associated with both spatial and temporal gradients of shear stress. Such gradients have been linked to the generation of atherosclerotic plaques. For in-vitro studies of endothelial cell responses, the sudden-expansion flow chamber has been widely used and described. A two-dimensional numerical simulation of the onset phase of flow through the chamber was performed. The wall shear stress action on the bottom plate was computed as a function of time and distance from the sudden expansion. The results showed that depending on the time for the flow to be established, significant temporal gradients occurred close to the second stagnation point of flow. Slowly ramping the flow over 15 s instead of 200 ms reduces the temporal gradients by a factor of 300, while spatial gradients are reduced by 23 percent. Thus, the effects of spatial and temporal gradients can be observed separately. In experiments on endothelial cells, disturbed flow stimulated cell proliferation only when flow onset was sudden. The spatial patterns of proliferation rate match the exposure to temporal gradients. This study provides information on the dynamics of spatial and temporal gradients to which the cells are exposed in a sudden-expansion flow chamber and relates them to changes in the onset phase of flow.
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Haidekker et al. (2001) studied this question.
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