Introduction

Endothelial cells (EC) lining blood vessel walls are exposed to both the wall shear stress (WSS) of blood flow and the circumferential strain (CS) and associated circumferential stress driven by the wall motion induced by pulsing pressure. Most in vitro studies of EC response to mechanical forces and mechanotransduction have focused on the either the WSS or the CS, but not their interaction. This is in spite of the fact that in the arterial circulation that is most susceptible to disease, the WSS and the CS are imposed concurrently. While there have been relatively few studies of simultaneous WSS and CS, several recent investigations have revealed that the response of endothelial cells to combined stresses is exquisitely sensitive to the temporal phase angle between them, suggesting that when they are applied in a highly out-of-phase manner, a pro-atherogenic response is produced, whereas when they are applied in-phase, the response is more favorable.

In this chapter we first review the physiological background on WSS and CS in the circulation to focus on those regions where their interaction is significant. In the process we uncover a fascinating pattern that suggests that the WSS and the CS are most asynchronous (out-of-phase temporally) in precisely those regions of the circulation where atherosclerosis is localized. This background is followed by a consideration of the in vitro experiments in which the WSS and the CS have been applied simultaneously to the EC. There we uncover dramatic influences of the phase angle between the WSS and the CS indicating that out-of-phase forces induce a pro-atherogenic EC phenotype. Animal experiments that are consistent with this view are reviewed and possible countermeasures are described.