LAPSE:2018.0438
Published Article
LAPSE:2018.0438
An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism
Frances Pool, Peter K. Sweby, Marcus J. Tindall
August 28, 2018
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.
Keywords
ordinary differential equation, SREBP-2
Suggested Citation
Pool F, Sweby PK, Tindall MJ. An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism. (2018). LAPSE:2018.0438
Author Affiliations
Pool F: Institute of Ophthalmology, University College London, Gower Street, London WC1E 6BT, UK [ORCID]
Sweby PK: Department of Mathematics and Statistics, University of Reading, Whiteknights, Reading RG6 6AX, UK
Tindall MJ: Department of Mathematics and Statistics, University of Reading, Whiteknights, Reading RG6 6AX, UK; Institute of Cardiovascular and Metabolic Research, University of Reading, Whiteknights, Reading RG6 6AA, UK
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Journal Name
Processes
Volume
6
Issue
8
Article Number
E134
Year
2018
Publication Date
2018-08-18
Published Version
ISSN
2227-9717
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PII: pr6080134, Publication Type: Journal Article
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LAPSE:2018.0438
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doi:10.3390/pr6080134
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Aug 28, 2018
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