Analysis of development of atherosclerosis based on the relationship between blood velocity profiles in vascular branch and the structure of endothelial cell

为探讨动脉粥样硬化的发生、发展和定位机制，我们研究了血管分支的血流速度分布与血管内皮细胞结构的关系。采用20 MHz超声脉冲多普勒测速仪和高分辨率回波超声装置，对肾动脉起始处的血流动力学进行了在体研究，测量了左肾动脉的速度分布和分叉几何形状。肾口处颅壁附近的流速模式，动脉粥样硬化病变是容易发展的，其特点是低的时间平均剪切率，流动分离，随时间变化的流动振荡。为探讨肾动脉血流模式对内皮细胞结构的影响，我们采用激光共聚焦显微镜观察了左肾动脉不同部位的内皮细胞结构。用罗丹明鬼笔环肽（RhodaminePhalloidin）和双苯酰亚胺（bisBenzimide）分别对细胞核内的F-肌动蛋白和DNA进行染色。在肾动脉起点远端的颅侧壁，血流呈再循环和双向振荡，内皮细胞和细胞核的形状相对较圆。细胞取向不均匀。在壁四血管直径远端的肾动脉的起源，其中血流具有抛物线向前的速度分布，内皮细胞和细胞核被拉长，并被定向到流动方向。内皮细胞中的应力纤维数量也增加，并且这些应力纤维也朝向流动方向。总之，肾动脉近端和远端区域的内皮细胞结构存在显著差异。因此，近端区域的独特血流模式可能通过改变内皮结构而引起动脉粥样硬化。

To analyze mechanisms of development and localization of atherosclerosis, we investigated the relationship between detailed blood velocity profiles in vascular branch and the structure of vascular endothelial cell. Using a 20MHz ultrasound pulsed Doppler velocimeter and a high-resolution echo ultrasound device, we studied in vivo hemodynamics at the origin of the renal artery measuring the velocity profiles and bifurcation geometry of left renal artery. The velocity pattern near the cranial wall at renal ostia, at which atherosclerosis lesions are prone to be developed, are characterized by low time-averaged shear rate, flow separation, and time-varying flow oscillation. To evaluate the possible contribution of blood flow pattern to the structure of endothelial cell in the renal artery, we investigated the structure of endothelial cells at different site of the left renal artery using a confocal laser scanning microscope. F-actin and DNA in nuclei were stained with rhodamine phalloidin and bisBenzimide, respectively. On the cranial side wall immediately distal to the origin of the renal artery, where blood flow showed recirculation and bi-directional oscillation, the shapes of endothelial cells and nuclei were relatively round. The cell orientation was not uniform. On the wall four-vascular diameters distal to the origin of the renal artery, where blood flow had a parabolic forward-velocity profile, endothelial cells and nuclei were elongated and were oriented to the flow direction. Also the number of stress fibers in the endothelial cell increased, and those stress fibers were also oriented to the flow direction. In conclusion, there were significant differences in the structure of endothelial cells in the proximal and distal regions of the renal artery. The unique blood flow pattern in the proximal region is thus likely to cause atherogenesis by modifying endothelial structure.