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Computational lipidology: predicting lipoprotein density profiles in human blood plasma

Abstract:

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond "bad" and "good" cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL), we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile) is calculated. As our main results, we (i) successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii) assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS), revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii) present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia.

18497853

Projects: A1.1: Central liver metabolism and its regulation under nutritional chal...

PLoS Comput. Biol.
PLoS Comput. Biol. 4(5): e1000079
24th May 2008

Katrin Hübner, Thomas Schwager, Karl Winkler, Jens-Georg Reich, Hermann-Georg Holzhütter

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[Karl Winkler] [Hermann-Georg Holzhütter]

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Views: 1520
  • Created: 4th Jan 2013 at 12:57
  • Last updated: 24th Oct 2013 at 16:22

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