Page 57 - Control Theory in Biomedical Engineering

44 Control theory in biomedical engineering

cardiovascular diseases (CVDs) and cholesterol level in blood plasma, cho-
lesterol content in food, and physical activity are not clearly understood.
Moreover, the physiological and molecular processes underlying cholesterol
homeostasis are still not definitively identified (Gold et al., 1992; Steinberg,
2004). However, it seems that there is a consensus on the relationship
between plasma cholesterol level and the risk of development and/or mor-
tality due to CVDs (Daniels et al., 2009). For ethical reasons, clinical trials
and trials conducted on animals are limited, whereas epidemiological studies
do not lead to unambiguous answers (McNamara, 2000). The results of
studies on animals do not always correspond to processes occurring in the
human body. An example of this is the research conducted on rabbits at
the beginning of the 20th century in which the relationship between the
formation of atherosclerotic lesions and a cholesterol-enriched diet was
demonstrated. It is worth noting here that rabbits are herbivorous animals
(a plant diet does not contain cholesterol) and hence their liver does not
show the dependence of the rate of cholesterol synthesis on the level of cho-
lesterol in the blood—but this relationship does exist in humans. In the case
of studies on other animals, only the differences in lipoprotein profiles were
observed in comparison to humans, and therefore the results of these studies
make it difficult to interpret the changes occurring in the human body
(McNamara, 2000).
A safe and relatively cheap way to expand the knowledge base on cho-
lesterol homeostasis is mathematical modeling. A well-built model is a mea-
sure of the understanding of the studied process, and should not only
reproduce the known reality but also give the possibility of prediction. With
regard to cholesterol homeostasis, it can help in gaining a more complete
understanding of the complex process and choosing optimal preventive
measures and treatments for a related disorder (Goodman et al., 1973; Cob-
bold et al., 2001; Kervizic and Corcos, 2008; Mc Auley et al., 2012; Mc
Auley and Mooney, 2015; Mishra et al., 2014; Hrydziuszko et al., 2014,
2015; Wrona et al., 2015; Toroghi et al., 2019).
Mathematical models of cholesterol homeostasis allowed for a better
understanding of this complex physiological process and indicated new pos-
sibilities in identifying the regulatory mechanisms that can be controlled
(Goodman et al., 1973; Cobbold et al., 2001; Kervizic and Corcos, 2008;
Wattis et al., 2008; Tindall et al., 2009; Mc Auley et al., 2012; Mc Auley
and Mooney, 2015; Hrydziuszko et al., 2014, 2015; Paalvast et al., 2015;
Wrona et al., 2015; Pool et al., 2018). Pharmacological agents that are cur-
rently in use act at a specific point in their regulatory mechanisms, but none