Biological Effects of Blood Flow induced Shear Stress
Shear stresses in the arterial system are generated by blood flow. Endothelial cells, which form the antithrombogenic intimal coating are subjected to this flow and to the corresponding stresses at the wall. A number of in vitro and in vivo experiments have demonstrated the effects of shear stress on endothelial cell morphology, cytoskeletal arrangement and migration. Additionally, shear stress has been implicated in vasoactivity in response to increasing blood flow, as well as in pathologies such as atherosclerosis. Atherosclerotic plaques typically originate in areas of low mean shear stresses, such as bifurcations.1
Shear stress affects endothelial morphology in a biphasic manner. Initially, endothelial cells subjected to fluid flow show an up regulation and rapid increase in the number of actin stress fibers. The cells then begin to transion to the steady state response, retracting and reducing the number of stress fibers while they begin to orient themselves parallel to the
direction of fluid flow. The degree
of retraction is directly correlated to shear stress magnitude. The steady state response is highlighted by respreading of the cells in an elongated ellipitcal fashon, with their major axes oriented parallel to the direction of flow. In addition, the actin stress fibers oriented themselves in a similar manner with only a few, mainly cortical fibers with random orientation.2
Shear stress also has profound effects on endothelial cell function. Increased shear stresses due to increased blood flow cause the production of nitrous oxide (NO). NO is a potent regulator of smooth muscle cell function, thus an increased shear stress causes vasodialation. Genetic expression is also affected by shear stress via upregulation of transcription factors, growth factors, enzymes and adhesion molecules, all of which can be either transiently or permanently activated. The degree and type of activation is finely dependant on very subtle variations in loading conditions, which suggests a very fine sensing mechanism. However, the lack of a classic “ligand-receptor” complex in the instance of biomechanical signaling has left the actual signaling mechanism open to debate.2 Two models that we shall consider here include: Glycocalyx Mediated and Integrin Mediated Mechanisms.
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1. Robert S. Reneman, Theo Arts and Arnold P.G. Hoeks. "Wall Shear Stress – an Important Determinant of Endothelial Cell Function and Structure – in the Arterial System in vivo."
Journal of Vascular Research 2006;43:251–269
2. Beata Wojciak-Stothard and Anne J. Ridley. "Shear stress–induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases." Journal of Cell Biology, Volume 161, Number 2, April 28, 2003 429–439
This page was last edited 10 June 2008