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An integrated mathematical model of cellular cholesterol biosynthesis and lipoprotein metabolism

Pool, F., Sweby, P. K. and Tindall, M. J. (2018) An integrated mathematical model of cellular cholesterol biosynthesis and lipoprotein metabolism. Processes, 6 (8). 134. ISSN 2227-9717

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To link to this item DOI: 10.3390/pr6080134

Abstract/Summary

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 {\it in vivo} setting via the incorporation of more dietary lipoprotein related processes and the need for further testing and parameterisation of {\it in silico} models of lipoprotein metabolism.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Science > School of Mathematical, Physical and Computational Sciences > Department of Mathematics and Statistics
ID Code:78571
Publisher:MDPI

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