Shear Stress–Mediated Arterial Remodeling in Atherosclerosis

Abstract

Under physiological conditions, chronic changes in blood flow stimulate compensatory changes in arterial size. This arterial remodeling process occurs during normal growth and development and contributes to the adaptive response to a variety of clinical situations. For example, repetitive increases in blood flow during exercise may stimulate expansive remodeling of conduit arteries in the limbs and heart,1 whereas chronic disuse of the lower extremities as a result of spinal cord injury is associated with constrictive remodeling of the femoral arteries.2 Uterine arteries display expansive remodeling during pregnancy and then undergo constrictive remodeling after delivery. Thus, dynamic remodeling of the arterial tree plays a critical role in maintaining the appropriate balance between tissue demand and blood supply throughout life. Article p 2826 A primary signal for arterial remodeling is shear stress, which is the frictional force at the endothelial surface produced by flowing blood.3,4 Shear stress relates directly to flow and blood viscosity and inversely to the third power of arterial radius.3 A macroscopic increase in blood flow increases local shear stress and stimulates arterial expansion until shear stress has been restored to baseline. Conversely, low shear stress leads to constrictive remodeling. This important homeostatic mechanism maintains shear stress in an appropriate range. When exposed to physiological levels of shear stress (15 to 40 dyne/cm2), endothelial cells appropriately elongate, align in the direction of flow, and maintain barrier function.4 Furthermore, normal shear stress promotes expression of vasodilator and antithrombotic factors, suppresses growth and proinflammatory factors, and generally maintains a state of vascular health. In contrast, low, oscillating, and disordered shear stress promotes the development of atherosclerosis. Expansive remodeling in response to chronic or repetitive increases in flow involves a coordinated sequence of events in the arterial wall, as has been extensively reviewed.3,5,6 Over a …