Morgan2016 - Dynamics of cholesterol metabolism and ageing
Ontology highlight
ABSTRACT:
Morgan2016 - Dynamics of cholesterol
metabolism and ageing
This model is described in the article:
Mathematically modelling the
dynamics of cholesterol metabolism and ageing.
Morgan AE, Mooney KM, Wilkinson SJ,
Pickles NA, Mc Auley MT.
BioSystems 2016 Jul; 145: 19-32
Abstract:
Cardiovascular disease (CVD) is the leading cause of
morbidity and mortality in the UK. This condition becomes
increasingly prevalent during ageing; 34.1% and 29.8% of males
and females respectively, over 75 years of age have an
underlying cardiovascular problem. The dysregulation of
cholesterol metabolism is inextricably correlated with
cardiovascular health and for this reason low density
lipoprotein cholesterol (LDL-C) and high density lipoprotein
cholesterol (HDL-C) are routinely used as biomarkers of CVD
risk. The aim of this work was to use mathematical modelling to
explore how cholesterol metabolism is affected by the ageing
process. To do this we updated a previously published
whole-body mathematical model of cholesterol metabolism to
include an additional 96 mechanisms that are fundamental to
this biological system. Additional mechanisms were added to
cholesterol absorption, cholesterol synthesis, reverse
cholesterol transport (RCT), bile acid synthesis, and their
enterohepatic circulation. The sensitivity of the model was
explored by the use of both local and global parameter scans.
In addition, acute cholesterol feeding was used to explore the
effectiveness of the regulatory mechanisms which are
responsible for maintaining whole-body cholesterol balance. It
was found that our model behaves as a hypo-responder to
cholesterol feeding, while both the hepatic and intestinal
pools of cholesterol increased significantly. The model was
also used to explore the effects of ageing in tandem with three
different cholesterol ester transfer protein (CETP) genotypes.
Ageing in the presence of an atheroprotective CETP genotype,
conferring low CETP activity, resulted in a 0.6% increase in
LDL-C. In comparison, ageing with a genotype reflective of high
CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the
model has illustrated the importance of CETP genotypes such as
I405V, and their potential role in healthy ageing.
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SUBMITTER: Amy Morgan
PROVIDER: MODEL1508170000 | BioModels | 2017-06-01
REPOSITORIES: BioModels
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