Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 441156
Title A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans
Author(s) Pas, N.C.A. van de; Woutersen, R.A.; Ommen, B. van; Rietjens, I.M.C.M.; Graaf, A.A. de
Source Journal of Lipid Research 53 (2012)12. - ISSN 0022-2275 - p. 2734 - 2746.
DOI https://doi.org/10.1194/jlr.M031930
Department(s) Sub-department of Toxicology
VLAG
WIMEK
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) high-density-lipoprotein - ester transfer protein - lemli-opitz-syndrome - apolipoprotein-b metabolism - lipid-metabolism - familial hypercholesterolemia - acyltransferase deficiency - estragole bioactivation - heart-disease - torcetrapib
Abstract Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was directly adapted from a PBK model for mice by incorporation of the reaction catalyzed by cholesterol ester transfer protein and contained 21 biochemical reactions and eight different cholesterol pools. The model was calibrated using published data for humans and validated by comparing model predictions on plasma cholesterol levels of subjects with 10 different genetic mutations (including familial hypercholesterolemia and Smith-Lemli-Opitz syndrome) with experimental data. Average model predictions on total cholesterol were accurate within 36% of the experimental data, which was within the experimental margin. Sensitivity analysis of the model indicated that the HDL cholesterol (HDL-C) concentration was mainly dependent on hepatic transport of cholesterol to HDL, cholesterol ester transfer from HDL to non-HDL, and hepatic uptake of cholesterol from non-HDL-C. jlr Thus, the presented PBK model is a valid tool to predict the effect of genetic mutations on cholesterol concentrations, opening the way for future studies on the effect of different drugs on cholesterol levels in various subpopulations in silico.-van de Pas, N. C. A., R. A. Woutersen, B. van Ommen, I. M. C. M. Rietjens, and A. A. de Graaf. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans. J. Lipid Res. 2012. 53: 2734-2746.
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