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A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy

Efremov, Y; Ermolaeva, A; Vladimirov, G; Gordleeva, S; Svistunov, A; Zaikin, A; Timashev, P; (2022) A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. PLoS ONE , 17 (6) , Article e0264903. 10.1371/journal.pone.0264903. Green open access

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Abstract

Cardiovascular diseases associated with high cholesterol (hypercholesterolemia) and low-density lipoproteins (LDL) levels are significant contributors to total mortality in developing and developed countries. Mathematical modeling of LDL metabolism is an important step in the development of drugs for hypercholesterolemia. The aim of this work was to develop and to analyze an integrated mathematical model of cholesterol metabolism in liver cells and its interaction with two types of drugs, statins and PCSK9 inhibitors. The model consisted of 21 ordinary differential equations (ODE) describing cholesterol biosynthesis and lipoprotein endocytosis in liver cells in vitro. The model was tested for its ability to mimic known biochemical effects of familial hypercholesterolemia, statin therapy, and PCSK9 inhibitors. The model qualitatively reproduced the well-known biology of cholesterol regulation, which confirms its potential for minimizing cellular research in initial testing of new drugs for cardiology.

Type: Article
Title: A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0264903
Publisher version: https://doi.org/10.1371/journal.pone.0264903
Language: English
Additional information: © 2022 Efremov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Antibodies, Monoclonal, Anticholesteremic Agents, Carcinoma, Hepatocellular, Cholesterol, Cholesterol, LDL, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipidemias, Lipoproteins, Liver Neoplasms, Models, Theoretical, PCSK9 Inhibitors, Proprotein Convertase 9
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10152264
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