Hao Wenrui, Friedman Avner
Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, United States of America.
Mathematical Biosciences Institute & Department of Mathematics, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2014 Mar 12;9(3):e90497. doi: 10.1371/journal.pone.0090497. eCollection 2014.
Atherosclerosis, the leading death in the United State, is a disease in which a plaque builds up inside the arteries. As the plaque continues to grow, the shear force of the blood flow through the decreasing cross section of the lumen increases. This force may eventually cause rupture of the plaque, resulting in the formation of thrombus, and possibly heart attack. It has long been recognized that the formation of a plaque relates to the cholesterol concentration in the blood. For example, individuals with LDL above 190 mg/dL and HDL below 40 mg/dL are at high risk, while individuals with LDL below 100 mg/dL and HDL above 50 mg/dL are at no risk. In this paper, we developed a mathematical model of the formation of a plaque, which includes the following key variables: LDL and HDL, free radicals and oxidized LDL, MMP and TIMP, cytockines: MCP-1, IFN-γ, IL-12 and PDGF, and cells: macrophages, foam cells, T cells and smooth muscle cells. The model is given by a system of partial differential equations with in evolving plaque. Simulations of the model show how the combination of the concentrations of LDL and HDL in the blood determine whether a plaque will grow or disappear. More precisely, we create a map, showing the risk of plaque development for any pair of values (LDL,HDL).
动脉粥样硬化是美国的主要死因,是一种动脉内形成斑块的疾病。随着斑块持续生长,流经管腔横截面不断减小处的血流剪切力会增加。这种力最终可能导致斑块破裂,形成血栓,并可能引发心脏病发作。长期以来,人们一直认识到斑块的形成与血液中的胆固醇浓度有关。例如,低密度脂蛋白(LDL)高于190毫克/分升且高密度脂蛋白(HDL)低于40毫克/分升的个体处于高风险状态,而低密度脂蛋白低于100毫克/分升且高密度脂蛋白高于50毫克/分升的个体则无风险。在本文中,我们建立了一个斑块形成的数学模型,其中包括以下关键变量:低密度脂蛋白和高密度脂蛋白、自由基和氧化低密度脂蛋白、基质金属蛋白酶(MMP)和组织金属蛋白酶抑制剂(TIMP)、细胞因子:单核细胞趋化蛋白-1(MCP-1)、干扰素-γ(IFN-γ)、白细胞介素-12(IL-12)和血小板衍生生长因子(PDGF),以及细胞:巨噬细胞、泡沫细胞、T细胞和平滑肌细胞。该模型由一个在不断演变的斑块中的偏微分方程组给出。模型模拟展示了血液中低密度脂蛋白和高密度脂蛋白浓度的组合如何决定斑块是会生长还是消失。更确切地说,我们创建了一个图表,显示了任何一对值(低密度脂蛋白,高密度脂蛋白)下斑块形成的风险。