A causal relationship between shear stress and atherosclerotic lesions in apolipoprotein E knockout mice assessed by ultrasound biomicroscopy

Abstract

The present study was undertaken to examine the hemodynamic state using the latest ultrasound biomicroscopy (UBM) technique and to investigate the effect of local shear stress on the development of atherosclerosis in the constrictive collar-treated carotid arteries of apolipoprotein E-deficient (apoE−/−) mice. Fifty-six male apoE−/− mice fed a high-lipid diet were divided into an interventional group ( n = 48) and the control group ( n = 8). Constrictive and nonconstrictive collars were placed around the carotid artery of the mice in the interventional group and the control group, respectively. The carotid lumen diameters and flow velocities were measured by UBM, and shear stress in the lesion region was calculated. Histopathology and electron microscopy were performed to observe the morphological changes in the carotid artery. In the region proximal to the constrictive collar, shear stress was significantly reduced 2 days after collar placement and remained low over time compared with the baseline level. In contrast, within the constrictive collar region, shear stress was increased significantly. Although endothelial permeability was enhanced in both regions, monocyte chemotaxis protein-1 (MCP-1) expression, macrophage infiltration, and atherosclerotic lesions were more prominent in the region proximal to the constrictive collar. Moreover, increased MCP-1 expression was observed as early as 2 days after constrictive collar placement, which preceded the morphological changes of the vessel wall. In conclusion, UBM offers a noninvasive and reliable technique for measuring shear stress in apoE−/− mice. Persistent low shear stress promotes endothelial permeability and enhances MCP-1 expression and macrophage recruitment, which were essential in the pathogenesis of atherosclerosis in apoE−/− mice.