Mathematical models of lipoprotein metabolism and kinetics: current status and future perspective

被引:3
作者
Lu, James [1 ]
Mazer, Norman A. [1 ]
Huebner, Katrin [2 ]
机构
[1] F Hoffmann La Roche Ltd, Clin Pharmacol, Basel, Switzerland
[2] Heidelberg Univ, BioQuant, Heidelberg, Germany
关键词
HDL; lipoprotein metabolism; lipoprotein structure models; mathematical modeling; mechanistic model; molecular dynamics; reverse cholesterol transport; statistical model; tracer kinetics; whole-body model; HIGH-DENSITY-LIPOPROTEINS; APOLIPOPROTEIN-A-I; CHOLESTEROL-METABOLISM; HDL METABOLISM; LIPIDOMICS; SIMULATION; VIVO;
D O I
10.2217/clp.13.52
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lipoprotein metabolism and kinetics comprises the time-dependent processes of synthesis, transformation and clearance of lipids, apolipoproteins and their assembled particles. By integrating and explaining the wealth of in vitro and clinical data available on lipoprotein metabolism and kinetics, mathematical models can provide novel insights into the underlying pathophysiology of lipid disorders, as well as quantify the effects of drugs intended for their treatment. In this article, we first discuss some basic principles of mathematical modeling in biology and drug development, and then review a number of recent publications in which different types of mathematical models have been used to investigate lipoprotein metabolism and kinetics. We conclude by posing a set of ten fundamental questions in this field that we believe mathematical modeling can potentially address, in the effort to develop novel and effective therapies for patients with high cardiovascular risk.
引用
收藏
页码:595 / 604
页数:10
相关论文
共 40 条
  • [1] [Anonymous], JOURNAL OF CLINICAL
  • [2] SAAM II: Simulation, Analysis, and Modeling Software for tracer and pharmacokinetic studies
    Barrett, PHR
    Bell, BM
    Cobelli, C
    Golde, H
    Schumitzky, A
    Vicini, P
    Foster, DM
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 1998, 47 (04): : 484 - 492
  • [3] Bergheanu SC, 2008, CURR MED RES OPIN, V24, P2477, DOI [10.1185/03007990802321709, 10.1185/03007990802321709 ]
  • [4] New model for kinetic studies of HDL metabolism in humans
    Chétiveaux, M
    Ouguerram, K
    Zair, Y
    Maugère, P
    Falconi, I
    Nazih, H
    Krempf, M
    [J]. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2004, 34 (04) : 262 - 267
  • [5] Computational models for analyzing lipoprotein profiles
    de Graaf, Albert A.
    van Schalkwijk, Daniel B.
    [J]. CLINICAL LIPIDOLOGY, 2011, 6 (01) : 25 - 33
  • [6] Molecular dynamics simulations and drug discovery
    Durrant, Jacob D.
    McCammon, J. Andrew
    [J]. BMC BIOLOGY, 2011, 9
  • [7] Funahashi Akira, 2003, Biosilico, V1, P159, DOI 10.1016/S1478-5382(03)02370-9
  • [8] Apolipoprotein A-I structural organization in high-density lipoproteins isolated from human plasma
    Huang, Rong
    Silva, R. A. Gangani D.
    Jerome, W. Gray
    Kontush, Anatol
    Chapman, M. John
    Curtiss, Linda K.
    Hodges, Timothy J.
    Davidson, W. Sean
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2011, 18 (04) : 416 - U44
  • [9] Applications and trends in systems biology in biochemistry
    Huebner, Katrin
    Sahle, Sven
    Kummer, Ursula
    [J]. FEBS JOURNAL, 2011, 278 (16) : 2767 - 2857
  • [10] Computational lipidology:: Predicting lipoprotein density profiles in human blood plasma
    Huebner, Katrin
    Schwager, Thomas
    Winkler, Karl
    Reich, Jens-Georg
    Holzhuetter, Hermann-Georg
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2008, 4 (05)