Heamodynamics of the Murine Aortic Arch: An Animal Specific Approach

Abstract

The inner wall of curved arteries as well as the area opposite the bifurcations of blood vessels are common sites of atherosclerotic lesion formation. This suggests that the focal nature of the disease may be partially determined by regional hemodynamics, of which wall shear stress (WSS) is thought to play a role. Located at the inner wall of blood vessels is the endothelium. The therapeutic potential of targeting the endothelium to treat artherosclerosis has not been realised, as the in vivo endothelial gene-expression response to WSS is not well characterised. This study develops computational flow simulations and novel experimental and surgical procedures to aid the investigation of the gene-expression response of the endothelium to local hemodynamics, in an animal specific context. The same mouse was used for each step: magnetic resonance imaging (MRI) and Doppler ultrasound were used to image a murine aortic arch in vivo and provide velocity data on boundary conditions, respectively. These data were used to perform computational blood flow simulations to determine the fluid-induced WSS throughout the aortic arch. The distribution of wall shear stress was then used to guide the laser microdissection of aortic endothelial cells from low and high shear stress regions. A specific distribution of blood-induced fluid wall shear stress was determined for each animal. The outer curved wall and the regions of the branching arteries where flow is divided were areas of relatively high shear stress. The inner curve of the aortic arch, as well as the region opposite of where the flow is divided by the branching arteries were areas of relatively low shear stress. Extension of the geometric model had relatively minor effects. The choice of boundary conditions had a significant effect on the WSS distribution. Immunohistolochemical staining using cluster of differentiation 31 and laser capture microdissection was effective in visualising and isolating, respectively, the endothelium from the murine aorta. This study has demonstrated a methodology for determining the endothelial gene-expression response to WSS, in a small animal population/patient specific context. A distribution of WSS and a discrete population of aortic endothelial cells can be obtained from the same mouse.