Investigation of the mechanism in localization of atherosclerosis by computational analysis of mass transfer from flowing blood to an arterial wall based on a true-to-scale anatomical model

为了阐明动脉粥样硬化和吻合口内膜增生等血管疾病在动脉系统中的定位机制，我们基于动物实验获得的真实比例的解剖模型，对致动脉粥样硬化性低密度脂蛋白(LDL)从流动的血液到动脉壁的质量传输进行了计算分析。为此，我们开发了一个测量真实动脉树脂铸型三维形态的实验系统，并开发了一种新的建模方法，从解剖学上构建用于计算的逼真模型。通过对动脉制备的组织学标本进行显微镜观察，测量动脉内膜增生发生的位置和内膜厚度的分布，用于构建计算模型。研究了血管壁切应力、管壁附近细微流型、管腔表面低密度脂蛋白浓度与血管内膜厚度等血流动力学参数之间的关系。结果发现，动脉管腔表面的低密度脂蛋白浓度在狭窄端远端、吻合口后跟和趾部局部升高，这些部位血流受扰，壁面剪应力相对较低，这一部位与观察到内膜增厚的部位很好地对应。这些结果表明，血流通过影响发生在血/内皮边界的低密度脂蛋白的浓度极化程度，在动脉粥样硬化和内膜增生的局部发生和发展中起重要作用。

To elucidate the mechanism in the localization of vascular diseases such as atherosclerosis and anastomotic intimal hyperplasia in the arterial system, we carried out computational analyses of mass transport of atherogenic low density lipoproteins (LDL) from flowing blood to an arterial wall based on true-to-scale anatomical models which were obtained by animal experiments creating a mild stenosis on rabbit common carotid arteries and an end-to-side anastomotic junction on dog common carotid arteries and harvesting them at different time postoperatively. To do that, we developed an experimental system measuring the 3-dimensional configuration of a resinous cast of real artery and a new modeling method to construct anatomically a realistic model for computation from the configuration of the arterial cast. We also measured the location where intimal hyperplasia occurred and the distribution of intimal thickness in the arteries which were used to construct the computational model by microscopic observation of histological specimens prepared from the arteries. Then the relationship among the hemodynamic properties such as wall shear stress and detailed flow patterns in the vicinity of the vessel wall, LDL concentration at the luminal surface of the vessel and the thickness of the intima was investigated. As the result, it was found that LDL concentration at the luminal surface of the artery was locally elevated distal to the apex of the stenosis and at heel and toe portions of the anastomotic junction where flow was disturbed and wall shear stress was relatively low, and that such a site corresponded well to the site where intimal thickening was observed. These results suggest that blood flow plays an important role in the localized pathogenesis and development of atherosclerosis and intimal hyperplasia by affecting the degree of concentration polarization of LDL which occurs at a blood/endothelium boundary.