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.

Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs

“…In addition, low-ESS regions co-localized with increased expression of VCAM and MCP-1, which are potent regulators of leukocyte adhesion and migration, respectively. These findings agree with prior studies in vitro and in small animal models of atherosclerosis [11,33–35]. Thus, in low-ESS arterial regions where the endothelium was more receptive to circulating cholesterol, intimal lipid accumulation was determined by the magnitude of hypercholesterolemia.…”

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall

“…Once the intimal matrix is established, infused LDL will be trapped there before reaching the medial layer. 32,39 Lipoprotein retention at sites exposed to disturbed laminar flow is not specific for LDL, as we show that HDL is retained at these sites as well. This is consistent with the unspecific nature of proteoglycan interactions, which has also been described for HDL 40 and complies with several previous studies showing that not only LDL but also several types of macromolecules, including model antigens and immune complexes, localize preferentially to natural predilection sites for atherosclerosis.…”

“…VSMCs treated with modified LDL secrete various proinflammatory cytokines and chemoattractants, eg, MCP-1 (monocyte chemoattractant protein-1). 38,39 Medial VSMCs in contact with retained LDL may thus function to attract the first inflammatory cells, and as the disease progresses, the intimal layer is expanded because of invasion of cells and matrix production. Once the intimal matrix is established, infused LDL will be trapped there before reaching the medial layer.…”

Mechanical stress related to brain atrophy in Alzheimer's disease

“…Atherosclerosis can increase arterial stiffness inducing damage of environment tissue [62]. Deletion of the ApoE gene, in turn, is responsible for the development of atherosclerosis due to its interaction with the shear stress on vessel walls [63].…”