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冠状动脉粥样斑块形成和发展的数学建模。

Mathematical modelling of atheroma plaque formation and development in coronary arteries.

机构信息

Applied Mechanics and Bioengineering, Aragón Institute of Engineering Research (I3A), University of Zaragoza, , Zaragoza, Spain.

出版信息

J R Soc Interface. 2013 Nov 6;11(90):20130866. doi: 10.1098/rsif.2013.0866. Print 2014 Jan 6.

Abstract

Atherosclerosis is a vascular disease caused by inflammation of the arterial wall, which results in the accumulation of low-density lipoprotein (LDL) cholesterol, monocytes, macrophages and fat-laden foam cells at the place of the inflammation. This process is commonly referred to as plaque formation. The evolution of the atherosclerosis disease, and in particular the influence of wall shear stress on the growth of atherosclerotic plaques, is still a poorly understood phenomenon. This work presents a mathematical model to reproduce atheroma plaque growth in coronary arteries. This model uses the Navier-Stokes equations and Darcy's law for fluid dynamics, convection-diffusion-reaction equations for modelling the mass balance in the lumen and intima, and the Kedem-Katchalsky equations for the interfacial coupling at membranes, i.e. endothelium. The volume flux and the solute flux across the interface between the fluid and the porous domains are governed by a three-pore model. The main species and substances which play a role in early atherosclerosis development have been considered in the model, i.e. LDL, oxidized LDL, monocytes, macrophages, foam cells, smooth muscle cells, cytokines and collagen. Furthermore, experimental data taken from the literature have been used in order to physiologically determine model parameters. The mathematical model has been implemented in a representative axisymmetric geometrical coronary artery model. The results show that the mathematical model is able to qualitatively capture the atheroma plaque development observed in the intima layer.

摘要

动脉粥样硬化是一种血管疾病,由动脉壁炎症引起,导致炎症部位的低密度脂蛋白(LDL)胆固醇、单核细胞、巨噬细胞和富含脂肪的泡沫细胞积聚。这个过程通常被称为斑块形成。动脉粥样硬化疾病的演变,特别是壁切应力对动脉粥样硬化斑块生长的影响,仍然是一个了解甚少的现象。本工作提出了一个数学模型来模拟冠状动脉中的动脉粥样硬化斑块生长。该模型使用纳维-斯托克斯方程和达西定律来模拟流体动力学,使用对流-扩散-反应方程来模拟管腔和内皮下的质量平衡,并使用 Kedem-Katchalsky 方程来模拟膜(即内皮)的界面耦合。流体和多孔域之间的界面的体积通量和溶质通量由三孔模型控制。该模型考虑了在早期动脉粥样硬化发展中起作用的主要物质和物质,即 LDL、氧化 LDL、单核细胞、巨噬细胞、泡沫细胞、平滑肌细胞、细胞因子和胶原。此外,还使用了来自文献的实验数据来生理确定模型参数。该数学模型已在代表性的轴对称几何冠状动脉模型中实现。结果表明,该数学模型能够定性地捕捉到内皮下观察到的动脉粥样硬化斑块发展。

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