A causal relationship between shear stress and atherosclerotic lesions in apolipoprotein E knockout mice assessed by ultrasound biomicroscopy
A causal relationship between shear stress and atherosclerotic lesions in apolipoprotein E knockout mice assessed by ultrasound biomicroscopy
复制标题
通过超声生物显微镜评估载脂蛋白 E 敲除小鼠的剪切应力与动脉粥样硬化病变之间的因果关系。
DOI：
10.1152/ajpheart.00308.2009
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发表时间：
2010-06-01
影响因子：
4.8
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Ding, Shi Fang;Ni, Mei;Zhang, Yun
本研究采用最新的超声生物显微镜（UBM）技术检测载脂蛋白E缺陷（apoE（-/-））小鼠颈动脉缩颈处理后的血流动力学状态，并探讨局部切应力对动脉粥样硬化发展的影响。将五十六只雄性apoE（-/-）小鼠分为干预组（n = 48）和对照组（n = 8）。分别在干预组和对照组小鼠颈动脉周围放置收缩性和非收缩性项圈。采用UBM测量颈动脉管腔直径和血流速度，计算病变区的切应力。组织学和电镜观察颈动脉形态学变化。在颈领近端区域，颈领放置后2天剪切应力显著降低，并且与基线水平相比，随着时间的推移保持较低。相反，在收缩领区域内，剪切应力显著增加。虽然在这两个地区的内皮渗透性增强，单核细胞趋化蛋白-1（MCP-1）的表达，巨噬细胞浸润，动脉粥样硬化病变更突出的区域近端的收缩领。此外，增加MCP-1的表达，观察到早在2天后，缩颈放置，之前的血管壁的形态学变化。总之，UBM为apoE（-/-）小鼠提供了一种非侵入性和可靠的剪切力测量技术。持续的低切应力促进内皮细胞的通透性，增强MCP-1的表达和巨噬细胞的募集，这在apoE（-/-）小鼠动脉粥样硬化的发病机制中是必不可少的。
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.