Budu-Grajdeanu Paula, Schugart Richard C, Friedman Avner, Valentine Christopher, Agarwal Anil K, Rovin Brad H
Mathematical Biosciences Institute, The Ohio State University, Columbus, OH, USA.
Theor Biol Med Model. 2008 Jan 23;5:2. doi: 10.1186/1742-4682-5-2.
In hemodialysis patients, the most common cause of vascular access failure is neointimal hyperplasia of vascular smooth muscle cells at the venous anastomosis of arteriovenous fistulas and grafts. The release of growth factors due to surgical injury, oxidative stress and turbulent flow has been suggested as a possible mechanism for neointimal hyperplasia.
In this work, we construct a mathematical model which analyzes the role that growth factors might play in the stenosis at the venous anastomosis. The model consists of a system of partial differential equations describing the influence of oxidative stress and turbulent flow on growth factors, the interaction among growth factors, smooth muscle cells, and extracellular matrix, and the subsequent effect on the stenosis at the venous anastomosis, which, in turn, affects the level of oxidative stress and degree of turbulent flow. Computer simulations suggest that our model can be used to predict access stenosis as a function of the initial concentration of the growth factors inside the intimal-luminal space.
The proposed model describes the formation of venous neointimal hyperplasia, based on pathogenic mechanisms. The results suggest that interventions aimed at specific growth factors may be successful in prolonging the life of the vascular access, while reducing the costs of vascular access maintenance. The model may also provide indication of when invasive access surveillance to repair stenosis should be undertaken.
在血液透析患者中，血管通路失败的最常见原因是动静脉内瘘和移植物静脉吻合处血管平滑肌细胞的内膜增生。手术损伤、氧化应激和湍流导致的生长因子释放被认为是内膜增生的一种可能机制。
在这项工作中，我们构建了一个数学模型，分析生长因子在静脉吻合处狭窄中可能发挥的作用。该模型由一个偏微分方程组组成，描述氧化应激和湍流对生长因子的影响、生长因子、平滑肌细胞和细胞外基质之间的相互作用，以及随后对静脉吻合处狭窄的影响，而静脉吻合处狭窄又反过来影响氧化应激水平和湍流程度。计算机模拟表明，我们的模型可用于预测作为内膜 - 管腔空间内生长因子初始浓度函数的通路狭窄情况。
所提出的模型基于致病机制描述了静脉内膜增生的形成。结果表明，针对特定生长因子的干预措施可能成功延长血管通路的使用寿命，同时降低血管通路维护成本。该模型还可能提供何时应进行侵入性通路监测以修复狭窄的指示。
