Exploring relationship between hypercholesterolemia and instability of atherosclerotic plaque - An approach based on a matrix population model.

Cardiovascular diseases have long been studied to identify their causal factors and counteract them effectively. Atherosclerosis, an inflammatory process of the blood vessel wall, is a common cardiovascular disease. Among the many well-known risk factors, hypercholesterolemia is undoubtedly a significant condition for atherosclerotic plaque formation and is linked to atherosclerosis on many levels, i.e. cell interactions, cytokines levels, diet, and lifestyle. Current studies suggest that controlling balance between proinflammatory (1) and anti-inflammatory (2) types of macrophages may be used for patient condition improvement and necrotic core reduction. This study considered the effects of hypercholesterolemia on the population dynamics of macrophages (0, 1, 2, foam cells) in atherosclerotic plaque. A mathematical model using a matrix approach to population dynamics was proposed and tested in various scenarios. In order to check model sensitivity and variability associated with error propagation, the uncertainty analysis was performed based on the Monte Carlo approach. Simulations of macrophage population dynamics provided the assessment of necrotic core development and plaque instability. Excess lipid levels emerged as the most critical factor for necrotic core development. However, plaque growth can be significantly slowed if macrophages and foam cells can maintain proper lipid levels. This balance may be disrupted by proinflammatory lipids that eventually will increase plaque size, what is also reflected by 1/2 dynamics. Hypercholesterolemia accelerates atherosclerosis development, leading to earlier cardiovascular incidents. results suggest that reducing lipid intake and portion of proinflammatory lipids is crucial to slowing plaque development and reducing rupture risk, all of which requires preserving fragile 1/2 balance. Targeting the inflammatory microenvironment and macrophage polarization represents a promising approach for atherosclerosis management.