A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy.
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 fo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0264903 |
| _version_ | 1818191470676410368 |
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| author | Yuri Efremov Anastasia Ermolaeva Georgiy Vladimirov Susanna Gordleeva Andrey Svistunov Alexey Zaikin Peter Timashev |
| author_facet | Yuri Efremov Anastasia Ermolaeva Georgiy Vladimirov Susanna Gordleeva Andrey Svistunov Alexey Zaikin Peter Timashev |
| author_sort | Yuri Efremov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T00:15:07Z |
| format | Article |
| id | doaj.art-ad0be7685d5348459a3c9d7876ac1ba6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T00:15:07Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ad0be7685d5348459a3c9d7876ac1ba62022-12-22T00:44:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176e026490310.1371/journal.pone.0264903A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy.Yuri EfremovAnastasia ErmolaevaGeorgiy VladimirovSusanna GordleevaAndrey SvistunovAlexey ZaikinPeter TimashevCardiovascular 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.https://doi.org/10.1371/journal.pone.0264903 |
| spellingShingle | Yuri Efremov Anastasia Ermolaeva Georgiy Vladimirov Susanna Gordleeva Andrey Svistunov Alexey Zaikin Peter Timashev A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. PLoS ONE |
| title | A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. |
| title_full | A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. |
| title_fullStr | A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. |
| title_full_unstemmed | A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. |
| title_short | A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy. |
| title_sort | mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy |
| url | https://doi.org/10.1371/journal.pone.0264903 |
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