The artery wall is lined by a monolayer of endothelial cells that provide the interface between flowing blood and the underlying layers of the blood vessel wall (Figure 1).  In large arteries like the aorta the vessel wall has three layers: the intimal layer containing the endothelial cells; the medial layer (smooth muscle cells); and the adventitial layer (fibroblasts).  The smallest vessels (capillaries) contain only the endothelial cells and not the underlying layers.  Endothelial cells are exposed to the mechanical forces of blood flow that include the fluid shear stress of flowing blood, the normal stress of blood pressure and the circumferential or hoop stress that resists the normal stress.

Figure 1. Hemodynamic Forces Acting on Artery Wall.

 

Mechanical forces have profound effects on endothelial cells as demonstrated in Figure 2 below. The left panel shows a monolayer of endothelial cells grown in static culture that have not been exposed to mechanical forces.  After exposure to 10 dyn/cm2 fluid flow shear stress for 24 hours (right) the cells are elongated and aligned in the direction of flow.

Figure 2. Remodeling of Endothelial Cells in Culture. Left Panel –static culture (no flow). Right Panel – Cultured cells exposed to 10 dyn/cm2 for 24 hrs (flow is from left to right).

Figure 2. Remodeling of Endothelial Cells in Culture. Left Panel –static culture (no flow). Right Panel – Cultured cells exposed to 10 dyn/cm2 for 24 hrs (flow is from left to right).

 

In addition to providing a surface that resists blood clotting, endothelial cells comprise a selective permeability barrier to the transport of biomolecules between blood and the underlying tissue. Mechanical forces such as blood flow shear stress have major influences on endothelial permeability, and our group has pioneered studies of the influence of fluid shear stress on endothelial permeability.  The production rates of many bioactive molecules by endothelial cells, such as the vasodilators nitric oxide and prostacyclin (PGI2), are highly responsive to mechanical forces.  The mechanosensors and transducers that are involved in these mechano-chemical processes have been the subject of intensive research efforts in recent decades.  Our group was among the first to show that the endothelial surface “sugar coating”, the glycocalyx, acts as a primary sensor of mechanical forces. Most recently, we’ve demonstrated that specific components of the glycocalyx are crucial to the regulation of shear-induced nitric oxide production as well as endothelial cell remodeling in response to fluid shear stress (Figure 2 above).

Endothelial cells experience fluid shear stress and circumferential stress (stretch) simultaneously. In large arteries such as the aorta, these forces are synchronous in time, whereas in the coronary arteries on the surface of the heart, they highly asynchronous.  Our group introduced a parameter termed the “stress phase angle” (SPA) to characterize temporal relationship between fluid shear stress and circumferential strain and we have shown that the SPA can be used to characterize regions of the circulation that are susceptible to vascular disease (atherosclerosis).

 NITRIC OXIDE PRODUCTIONPROSTACYCLIN PRODUCTION     STRESS PHASE ANGLE