Shear Stress Gradients Remodel Endothelial Monolayers in Vitro via a Cell Proliferation-Migration-Loss Cycle

Abstract

Wall shear stress has been implicated in the genesis of atherosclerosis because a strong correlation exists between the location of developing arterial lesions and regions where particular gradients in stress occur. Studying the behavior of endothelial cells in such regions may contribute to our understanding of the disease etiology. We report the detailed migratory history of endothelial cells subjected to large shear stress gradients caused by a surface protuberance in an in vitro model system. The history of cell migration, cell division, and cell loss from the surface was continuously monitored in confluent human umbilical vein endothelial cell monolayers for 48 hours after the onset of flow. Individual cells were tracked using time-lapse video microscopy. In contrast to a uniform laminar flow field in which cells were observed to continually rearrange their relative position with no net migration, in a disturbed flow field there was a net migration directed away from the region of high shear gradient. This organized migration pattern under disturbed flow conditions was accompanied by more than a twofold increase in cell motility. In addition, cell division increased in the vicinity of the flow separation (maximum shear stress gradient of 34 dyne/cm2 per mm) whereas cell loss was increased upstream and downstream in the regions where the shear gradient diminishes. These data suggest a steady cell proliferation-migration-loss cycle and indicate that local shear stress gradient may play a key role in the morphological remodeling of the vascular endothelium in vivo.

Vascular Endothelium, Hemodynamic Forces, and Atherogenesis

“…Using this in vitro spatial disturbed flow model, dramatic differences in endothelial cell shape, migration, and proliferation have been demonstrated in association with disturbed flow as compared with uniform laminar flow. 34 In addition, significant differences in endothelial expression of Connexin43 at the level of mRNA and protein, and concomitant changes in cell-cell communication via gap junctions, also have been correlated with the presence of shear stress gradients in this model. 35 Recent studies suggest that these in vitro observations may indeed have a counterpart in vivo.…”

The spectral/hp element modelling of steady flow in non‐planar double bends

“…Many researchers have investigated pressure, velocity distributions, velocity gradient and the influence of steady and unsteady shear stresses and the gradient of wall shear stress in steady or unsteady flows on the wall or on the blood cell in vascular configurations [9][10][11]. These mechanical factors are involved in the accumulation of lipids, a cause of atherosclerosis.…”

The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells

“…It has been shown that shear stress induces EC monolayer remodeling, e.g., increase of stress fibers and alterations in gene expression (7,8). Shear stress can modulate EC migration in wounding area and vascular stent surface (9)(10)(11)(12), but the kinetics and molecular mechanism of EC migration in response to shear stress remain to be determined.…”