The movement of blood in the systemic and pulmonary circulations influences every cell of those vascular systems, but its most immediate mechanical effect is on the endothelium. The endothelium is well recognized as a hemodynamic mechanotransduction interface that in turn influences the biology of the vessel and its physiological responses. Furthermore, in arteries, hemodynamic forces are associated with endothelial phenotypes that predispose specific sites to focal atherogenesis. This chapter considers the relationships between hemodynamics and endothelial phenotypes and reviews our current understanding of the broader mechanisms of endothelial mechanosensing and signal transduction as they relate to arterial physiology and pathology. The microcirculation and post-capillary venous return – regions in which flow effects on leukocyte interactions with the endothelium occur in the context of acute inflammation – are considered elsewhere in this volume (see Chapter 114).

THE ENDOTHELIUM IS HIGHLY RESPONSIVE TO LOCAL HEMODYNAMICS

A feature common to all endothelial cells (ECs) studied in a variety of vascular locations and cell cultures is the ability to respond to local changes of blood flow, particularly to acute and sustained changes of hemodynamic shear stresses that deform the cell (1–4). The endothelia of arteries and heart valves are generally subjected to the highest magnitudes and variations in hemodynamic forces. Arterial hemodynamics has received the most experimental scrutiny, in part because of the correlative relationships that exist between certain hemodynamic characteristics and atherosclerosis. However, models and measurements of flow complexities around the heart valves recently have focused on molecular investigations of the role of hemodynamics in regulating valve endothelial pathophysiology; both are considered here.