Two-compartment model as a teaching tool for cholesterol homeostasis

Abstract

Cholesterol is a vital structural and functional molecule in the human body that is only slightly soluble in water and therefore does not easily travels by itself in the bloodstream. To enable cholesterol's targeted delivery to cells and tissues, it is encapsulated by different fractions of lipoproteins, complex particles containing both proteins and lipids. Maintaining cholesterol homeostasis is a highly regulated process with multiple factors acting at both molecular and tissue levels. Furthermore, to regulate the circulatory transport of cholesterol in lipoproteins, the amount of cholesterol present depends on and is controlled by cholesterol dietary intake, de novo synthesis, usage, and excretion; abnormal and/or unbalanced cholesterol levels have been shown to lead to severe outcomes, e.g., cardiovascular diseases. To investigate cholesterol transport in the circulatory system, we have previously developed a two-compartment mathematical model. Here, we show how this model can be used as a teaching tool for cholesterol homeostasis. Using the model and a hands-on approach, students can familiarize themselves with the basic components and mechanisms behind balanced cholesterol circulatory transport as well as investigate the consequences of and countermeasures to abnormal cholesterol levels. Among others, various treatments of high blood cholesterol levels can be simulated, e.g., with commonly prescribed de novo cholesterol synthesis inhibitors.