Mechanical force transmission via the cytoskeleton in vascular endothelial cells

By virtue of its anatomic location, the vascular endothelium is constantly exposed to a highly dynamic mechanical stress environment due to the pulsatile nature of blood flow. The mechanical stress field on the vascular endothelial cell (EC) surface consists of three components: tangential shear forces due to the flow of viscous blood, normal pressure forces due to endovascular pressure, and circumferential stretch forces due to transmural pressure difference. The mechanical stresses to which a particular population of ECs is subjected depends strongly on the vascular bed from which the cells are derived and the location of the cells within that bed. In the microvasculature, blood pulsatility is highly damped and the flow is quasi-steady. Consequently, ECs in microvessels experience a nearly constant level of shear stress in time, even though the magnitude of that shear stress depends strongly on microvessel size. In medium and large blood vessels, on the other hand, blood flow is highly unsteady, leading to large and periodic variations in the mechanical stresses experienced by the endothelium during the course of the cardiac cycle. Changes in activity level, for instance rest vs. exercise, further add to these temporal variations in the mechanical stress field. In addition, the complex vascular geometry, which includes branches, bifurcations and extensive curvature, induces disturbances in the vascular flow field which often take the form of flow separation and recirculation zones within which the mechanical stress field is severely altered. Therefore, the endothelium in medium and large blood vessels is additionally subjected to large spatial gradients in the mechanical stress field. In these vessels, there is also a difference in the mechanical stress environment between arteries and veins due to the large difference in transmural blood pressure between the two types of blood vessels.