The endothelial cell layer that lines all blood vessels is continuously exposed to mechanical forces imposed by flowing blood. These forces include fluid shear stress on the endothelial surface and solid stretching forces imparted to the endothelial cells by deformations of the elastic vessel wall in response to pressure variations. These two forces (shear and stretch) may be out of phase in time due to the complex interactions of pressure and flow that occur in different regions of the circulation. The result is a complex, time varying, force field applied to the endothelial cells which can have a significant influence on the biology of the cells. The nature of these force patterns on endothelial cells is believed to play an important role in the development of atherosclerosis, a degenerative disease of arteries that underlies heart attacks and strokes.

Our group has carried out in vitro measurements of fluid mechanical shear stress and circumferential stretch (strain) in curved and branched artery models using laser Doppler velocimetry, photochromic dye dispersion and other techniques which have allowed us to consider the influences of non-Newtonian blood rheology, vessel wall elasticity, flow pulsatility and complex geometry. Our experimental work on arterial flows is complemented by theoretical studies using perturbation methods and computer simulations employing local computer networks and national supercomputers. These studies reveal certain characteristics of the wall shear stress and circumferential stretch which are unique to atherogenic regions of the circulation.

To determine the biological effects of interacting fluid wall shear stress and circumferential stretch on endothelial cells we have developed an in vitro experimental model using cultured endothelial cells grown on the inside surface of an elastic silicone tube and exposed to complex fluid mechanical environments in a mock circulatory system. We have been able to demonstrate dramatic differences in the production of vasoactive compounds by endothelial cells due to differences in the phasic relationship between applied shear stress and circumferential stress. Studies in progress will determine how these altered mechanical environments affect the production of a wide range of vasoactive molecules and the expression of genes which control vascular function as well as the expression and localization of certain junction proteins and cell cycle processes.