Abstract:
:Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein size-classes but exactly how each small class relates to disease risk is difficult to clear up. Because relating physiological process status to disease risk seems promising, we propose investigating how lipoprotein production, lipolysis, and uptake processes depend on particle size. To do this, we introduced a novel model framework (Particle Profiler) and evaluated its feasibility. The framework was tested using existing stable isotope flux data. The model framework implementation we present here reproduced the flux data and derived lipoprotein size pattern changes that corresponded to measured changes. It also sensitively indicated changes in lipoprotein metabolism between patient groups that are biologically plausible. Finally, the model was able to reproduce the cholesterol and triglyceride phenotype of known genetic diseases like familial hypercholesterolemia and familial hyperchylomicronemia. In the future, Particle Profiler can be applied for analyzing detailed lipoprotein size profile data and deriving rates of various lipolysis and uptake processes if an independent production estimate is given.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
van Schalkwijk DB,de Graaf AA,van Ommen B,van Bochove K,Rensen PC,Havekes LM,van de Pas NC,Hoefsloot HC,van der Greef J,Freidig APdoi
10.1194/jlr.M800354-JLR200subject
Has Abstractpub_date
2009-12-01 00:00:00pages
2398-411issue
12eissn
0022-2275issn
1539-7262pii
M800354-JLR200journal_volume
50pub_type
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