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一种新的相关关系,用于将渗漏连接纳入动脉粥样硬化病变起始的宏观建模中。

A new correlation for inclusion of leaky junctions in macroscopic modeling of atherosclerotic lesion initiation.

机构信息

Department of Chemical Engineering, Jundi-Shapur University of Technology, Dezful, Iran.

出版信息

J Theor Biol. 2013 Jul 21;329:94-100. doi: 10.1016/j.jtbi.2013.02.018. Epub 2013 Mar 15.

Abstract

Vascular endothelium cells are the main barriers between vessel wall and blood flow; they play an essential role in the progression of atherosclerosis. Various experimental and computational studies have been carried out to identify the pathways and mechanisms by which Low Density Lipoprotein (LDL) transfers through the endothelium cells. The most conventional hypothesis in LDL transfer is the presence of leaky junctions. Leaky junctions are large pores in endothelium cells associated with cell mitosis or apoptosis. Although some studies have microscopically modeled leaky junctions, none however have evaluated their effects in a macroscopic level modeling. In this study, a new approach is proposed to consider the presence of the leaky junction as the main pathway in LDL transport from the lumen into the arterial wall. LDL transport in macroscopic scale is simulated in a simplified axisymmetric model and Staverman filtration coefficient (SFC) is used as a measurement criterion for estimating the amount of leaky junctions. According to the results, decreasing SFC corresponds to decreasing the resistance of endothelium cells. In other words, an increase in the number of leaky junctions causes an increase in the LDL concentration inside the arterial wall. Additionally, a new correlation is presented for evaluating the fraction of leaky junctions in the endothelial cells by comparing the results of macroscopic and microscopic models. This correlation accredits each SFC to a specified fraction of leaky junction in the endothelial cells. Therefore, it can be used for the inclusion of leaky junctions in the macroscopic modeling without incorporating any of the complications that are raised by the microscopic modeling studies. This correlation has important implications in the modeling of the atherosclerosis lesions propagation.

摘要

血管内皮细胞是血管壁和血流之间的主要屏障;它们在动脉粥样硬化的发展中起着至关重要的作用。已经进行了各种实验和计算研究,以确定低密度脂蛋白 (LDL) 通过内皮细胞转移的途径和机制。LDL 转移的最传统假设是存在渗漏连接。渗漏连接是内皮细胞中与细胞有丝分裂或细胞凋亡相关的大孔。尽管一些研究已经在显微镜下模拟了渗漏连接,但没有一个研究评估了它们在宏观水平建模中的影响。在这项研究中,提出了一种新方法来考虑渗漏连接作为 LDL 从管腔转移到动脉壁的主要途径。在简化的轴对称模型中模拟宏观尺度的 LDL 转运,并使用 Staverman 过滤系数 (SFC) 作为估计渗漏连接数量的测量标准。根据结果,SFC 的降低对应于内皮细胞阻力的降低。换句话说,渗漏连接数量的增加会导致动脉壁内 LDL 浓度的增加。此外,通过比较宏观和微观模型的结果,提出了一种新的相关性来评估内皮细胞中渗漏连接的分数。该相关性将每个 SFC 分配给内皮细胞中特定的渗漏连接分数。因此,它可用于在不引入微观建模研究提出的任何复杂性的情况下,将渗漏连接纳入宏观建模中。该相关性对动脉粥样硬化病变传播的建模具有重要意义。

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