A two-phase model of early atherosclerotic plaque development with LDL toxicity effects.

Atherosclerosis is a chronic inflammatory cardiovascular disease in which fatty plaque builds up inside an artery wall. Early atherosclerotic plaque development is typically characterized by inflammatory tissue primarily consisting of macrophages and foam cells. In this article, we present a free boundary biphasic model of early atherosclerotic plaque to investigate the effects of low-density lipoprotein (LDL) toxicity on plaque development. The study examines the roles of cytokines (particularly monocyte chemoattractant protein-1) and oxidized low-density lipoprotein (oxLDL) in the recruitment of monocytes and the formation of foam cells, respectively. The ingestion of oxLDL by macrophages results in the accumulation of intracellular cholesterol, and its excessive level becomes toxic to foam cells, leading to cell death beyond a threshold. We examine how intracellular cholesterol-induced toxicity impacts plaque development. We find that the plaque initially grows rapidly, and the growth rate eventually declines due to cholesterol-induced toxicity. Parameters associated with toxicity-induced cell death play a key role in reducing the plaque growth rate by promoting cell death. We show that raising the toxicity threshold increases the volume fraction of inflammatory cells, thereby accelerating plaque growth. Investigations of the flux parameters reveal that increased cytokine flux enhances plaque growth, whereas higher oxLDL flux reduces the growth rate. A detailed analysis of the model presented in this article provides critical insights into the various biochemical and cellular mechanisms behind early plaque development.