White, C.R.*, Haidekker, M.*, Bao, X, Frangos, J.A. (2001)

Temporal gradients in shear stress, but not spatial gradients or steady shear, induce endothelial cell proliferation.
Circulation 2001 103:2508-2513

Background - The effect of temporal and spatial gradients in shear on primary human endothelial cells (HUVEC) proliferation was investigated. The sudden expansion flow chamber (SEFC) model was used to differentiate the effect of temporal gradients in shear from that of spatial gradients. With a sudden onset of flow, cells are exposed to both temporal and spatial gradients of shear. The temporal gradients can be eliminated by slowly ramping up the flow.
Methods & Results - HUVEC proliferation in the SEFC remained unstimulated when the onset of flow was slowly ramped. Sudden-onset of flow stimulated a 105% increase of HUVEC proliferation (relative to ramped onset) within the region of flow reattachment. To further separate temporal and spatial gradients, a conventional parallel plate flow chamber was utilized. A single 0.5 second impulse of 10 dyne/cm2 increased HUVEC proliferation 54%±3 relative to control. When flow was slowly ramped over 30 seconds, HUVEC proliferation was not significantly different from controls. Steady laminar shear over 20 minutes inhibited HUVEC proliferation relative to controls regardless of step (36%±8) or ramp (21%±5) onsets of flow.
Conclusions - The results indicate that temporal gradients in shear stress stimulate endothelial cell proliferation, whereas spatial gradients affect endothelial proliferation no differently than steady uniform shear stress.

 

View Supplemental movie depecting the sudden onset phase of flow in the SEFC
NOTE: This is a very large file (1.6MB)

 

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* Drs White and Haidekker are joint primary authors of this work.