ABSTRACT
Cells of the vascular system are constantly exposed to mechanical (hemodynamic) forces due to the flow of blood. The forces generated in the vasculature include the frictional force or a fluid shear stress caused by blood flowing tangentially across the endothelium, a tensile stress caused by circumferential vessel wall deformations, and a net normal stress caused by a hydrodynamic pressure differential across the vessel wall. We will restrict our discussion to examining fluid shear stress modulation of vascular cell function. The endothelium is a biologically active monolayer of cells providing an interface between the flowing blood and tissues of the body. It can synthesize and secrete a myriad of vasoconstrictors, vasodilators, growth factors, fibrinolytic factors, cytokines, adhesion molecules, matrix proteins, and mitogens that modulate many physiologic processes, including wound healing, hemostasis, vascular remodeling, vascular tone, and immune and inflammatory responses. In addition to humoral stimuli, it is now well accepted that endothelial cell synthesis and secretion of bioactive molecules can be regulated by the hemodynamic forces generated by the local blood flow. These forces have been hypothesized to regulate neovascularization and the structure of the blood vessel [Hudlicka, 1984]. Clinical findings further show that arterial walls undergo an endothelium-dependent adaptive response to changes in blood flow, with blood vessels in high flow regions tending to enlarge and vessels in the low flow region having reduced lumen diameter, thereby maintaining a nearly constant shear stress at the vessel wall [Zarins et al., 1987]. In addition to playing an active role in the normal vascular biology, hemodynamic
forces have also been implicated in the pathogenesis of a variety of vascular diseases. Atherosclerotic lesion-prone regions, characterized by the incorporation of Evans blue dye, enhanced accumulation of albumin, fibrinogen, and LDL, increased recruitment of monocytes, and increased endothelial turnover rates exhibit polygonal endothelial cell morphology typically seen in a low-shear environment, as opposed to nonlesion regions that have elongated endothelial cells characteristic of high-shear regions [Nerem, 1993].
