Effect of Disturbed Blood Flow on Endothelial Cell Gene Expression
A Role for Changes in RNA Processing
Conduit arteries deliver oxygenated blood to tissues. When the demand for oxygen increases in a tissue, such as in muscle during exercise, blood flow and velocity increases. Conduit artery diameter increases in this setting. This physiological response occurs because endothelial cells sense shear forces and respond by modulating the production of nitric oxide, a key endothelial-derived vasodilator. Shear stress is the frictional force exerted by flowing blood on endothelial cells and is dependent on the velocity at the blood boundary layer.1 In arteries, shear stress varies throughout the cardiac cycle, being high during systole and low during diastole, with a time-averaged shear stress typically 10 to 20 dyne/cm2. When the velocity of blood changes, it is known that arteries dilate or contract, which serves to normalize wall shear stress to a physiological level of 10 to 20 dyne/cm2. If flow is altered for a prolonged period, arteries undergo an inward or outward remodeling process that permanently normalizes wall shear stress.
See accompanying article on page 2042
In straight arterial segments, blood flow is uniform laminar, that is, parabolic and unidirectional throughout the cardiac cycle. In contrast, at inner curvatures, bifurcations and branch points flow is disturbed laminar, meaning that it is complex but predictable, with the directionality reversing during diastole and a stagnation point moving with the cardiac cycle. The time-averaged shear stress is low in these regions. Turbulent flow, characterized by irregular, unpredictable, or chaotic fluctuations, occurs rarely in humans and almost never in rodents because flow is rapidly stabilized in vessels with a small diameter.
Although disturbed flow is prevalent at specific anatomic locations, the artery does not remodel perhaps because these regions include …