SYNERGISTIC EFFECTS OF FLUID SHEAR-STRESS AND CYCLIC CIRCUMFERENTIAL STRETCH ON VASCULAR ENDOTHELIAL-CELL MORPHOLOGY AND CYTOSKELETON

The development of atherosclerosis is thought to be initiated by a dys functional state of the vascular endothelium. The proposal that mechan ical forces play a role in the localization of this disease has led re searchers to develop in vitro models to assess their effects on cultur ed endothelial cells. The arterial endothelium is exposed simultaneous ly to circumferential hoop stretch and wall shear stress, yet previous investigations have focused on the isolated effects of either cyclic stretch or shear stress. The influence of physiological levels of comb ined shear stress and hoop stretch on the morphology and F-actin organ ization of bovine aortic endothelial cells was investigated. Cells sub jected for 24 hours to shear stresses higher than 2 dyne/cm(2) or to h oop stretch greater than 2% elongated significantly compared with unst ressed controls and oriented along the direction of flow and perpendic ular to the direction of stretch. Exposure to more than 4% stretch sig nificantly enhanced the responses to shear stress. Both shear stress a nd hoop stretch induced formation of stress fibers that were aligned w ith the cells' long axes. Simultaneous exposure to both stimuli appear ed to enhance stress fiber size and alignment. These results indicate that shear stress and hoop stretch synergistically induce morphologica l changes in endothelial cells, which suggests that circumferential st rain might modulate sensitivity of endothelial cells towards shear str ess.