Wall Shear Stress and Arterial Wall Remodeling

Wall shear stress is the tangential drag force produced by blood moving across the endothelial surface. It is a function of the velocity gradient of blood near the endothelial surface. Its magnitude is directly proportional to blood flow and blood viscosity and inversely proportional to the cube of the radius. Thus, a small change in the radius of a vessel will have a large effect on wall shear stress. Wall shear stress regulates arterial wall remodeling. Arteries enlarge in response to high shear stress [Zarins, Masuda ( pdf )]. Atherosclerotic plaques localize preferentially in regions of low shear stress and not in regions of high shear stress. Furthermore, decreased shear stress induces intimal thickening in the vessel which had adapted to high flow [ Zhuang ]. Subnoemal shear stress also results in endothelial apoptosis [ Sho , pdf ]. RT-PCR has demonstrated an increased transcription of basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF) prior to measurable flow induced arterial enlargement [ Singh ]. In a model of transgenic mice with c-fos linked to a lac-z reporter gene, early c-fos expression was detected in endothelial cells during the first 3 days. Thus, increased shear stress results in the expression of arterial wall proto-oncogenes prior to the onset of flow induced arterial enlargement [Andrew]. The role of nitric oxide (NO) in chronic flow-induced adaptive enlargement was demonstrated in rat femoral AVF model by means of L-NAME inhibition of NO [ Guzman ].

Studies of molecular modulators of flow induced aortic enlargement have been our major efforts in the recent years. Using a mouse aorta-vena cava fistula model, a gross view of the fistula site is available [ link to photo ]. we are defining the molecular modulators of aortic enlargement and to characterize the cellular and extracellular matrix adaptive remodeling process, involving growth factors and apoptosis related issues.

Our laboratory has a long time collaboration with the vascular biology laboratory in the Second Department of Pathology, Akita University , Japan, chaired by Professor Hirotake Masuda , MD, PhD. Our collaboration is in full swing and we hope we will achieve more fundamental understanding of the vascular biology in the years to come.