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Processes 2018, 6(8), 134; https://doi.org/10.3390/pr6080134

An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism

1
Institute of Ophthalmology, University College London, Gower Street, London WC1E 6BT, UK
2
Department of Mathematics and Statistics, University of Reading, Whiteknights, Reading RG6 6AX, UK
3
Institute of Cardiovascular and Metabolic Research, University of Reading, Whiteknights, Reading RG6 6AA, UK
Current address: Department of Mathematics and Statistics, University of Reading, Whiteknights, Reading RG6 6AX, UK.
*
Author to whom correspondence should be addressed.
Received: 29 June 2018 / Revised: 8 August 2018 / Accepted: 10 August 2018 / Published: 18 August 2018
(This article belongs to the Special Issue Methods in Computational Biology)
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Abstract

Cholesterol regulation is an important aspect of human health. In this work we bring together and extend two recent mathematical models describing cholesterol biosynthesis and lipoprotein endocytosis to create an integrated model of lipoprotein metabolism in the context of a single hepatocyte. The integrated model includes a description of low density lipoprotein (LDL) receptor and cholesterol synthesis, delipidation of very low density lipoproteins (VLDLs) to LDLs and subsequent lipoprotein endocytosis. Model analysis shows that cholesterol biosynthesis produces the majority of intracellular cholesterol. The availability of free receptors does not greatly effect the concentration of intracellular cholesterol, but has a detrimental effect on extracellular VLDL and LDL levels. We test our model by considering its ability to reproduce the known biology of Familial Hypercholesterolaemia and statin therapy. In each case the model reproduces the known biological behaviour. Quantitative differences in response to statin therapy are discussed in the context of the need to extend the work to a more in vivo setting via the incorporation of more dietary lipoprotein related processes and the need for further testing and parameterisation of in silico models of lipoprotein metabolism. View Full-Text
Keywords: ordinary differential equation; SREBP-2 ordinary differential equation; SREBP-2
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Pool, F.; Sweby, P.K.; Tindall, M.J. An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism. Processes 2018, 6, 134.

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