August E, Parker K H, Barahona M
Department of Bioengineering, Imperial College London, South Kensington Campus, London, United Kingdom.
Bull Math Biol. 2007 May;69(4):1233-54. doi: 10.1007/s11538-006-9132-6. Epub 2007 Mar 3.
We present a dynamical model of lipoprotein metabolism derived by combining a cascading process in the blood stream and cellular level regulatory dynamics. We analyse the existence and stability of equilibria and show that this low-dimensional, nonlinear model exhibits bistability between a low and a high cholesterol state. A sensitivity analysis indicates that the intracellular concentration of cholesterol is robust to parametric variations while the plasma cholesterol can vary widely. We show how the dynamical response to time-dependent inputs can be used to diagnose the state of the system. We also establish the connection between parameters in the system and medical and genetic conditions.
我们提出了一种脂蛋白代谢动力学模型,该模型通过结合血流中的级联过程和细胞水平的调节动力学推导得出。我们分析了平衡点的存在性和稳定性,并表明这个低维非线性模型在低胆固醇状态和高胆固醇状态之间表现出双稳态。敏感性分析表明,细胞内胆固醇浓度对参数变化具有鲁棒性,而血浆胆固醇则可能有很大变化。我们展示了如何利用对随时间变化的输入的动态响应来诊断系统状态。我们还建立了系统参数与医学和遗传状况之间的联系。