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arXiv · 2304.02587

A Two-Phase Model of Early Atherosclerotic Plaque Development with LDL Toxicity Effects

Abstract

Atherosclerosis is a chronic inflammatory cardiovascular disease in which fatty plaque is built inside an artery wall. Early atherosclerotic plaque development is typically characterized by inflammatory tissues primarily consisting of foam cells and macrophages. We present a biphasic model that explores early plaque growth to emphasize the role of cytokines (particularly, Monocyte Chemoattractant Protein-1) and oxidized low-density lipoprotein (oxLDL) in monocyte recruitment and foam cell production, respectively. The plaque boundary is assumed to move at the same speed as the inflammatory tissues close to the periphery. This study discusses the oxLDL cholesterols recruitment inside intima and their internalization by the inflammatory cells. Excessive intracellular cholesterol accumulation becomes toxic to macrophage foam cells, leading to cell death beyond a threshold. Our findings reveal that initially, the plaque evolves rapidly, and the growth rate eventually reduces because of the cholesterol-induced toxicity. The present study manifests that higher oxLDL cholesterol flux reduces plaque growth rate, while elevated cytokines flux promotes the corresponding plaque growth behaviour. Between oxLDL cholesterol and intracellular cholesterol, the second one is much more effective towards the growth of inflammatory tissue. The cholesterol-based toxicity-induced cell death parameters are crucial in flattening the plaque growth profile. A detailed analysis of the model presented in this article provides critical insights into the various biochemical and cellular mechanisms behind early plaque development.

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Abdush Salam Pramanik, Bibaswan Dey, G. P. Raja Sekhar. 2023-04-05. A Two-Phase Model of Early Atherosclerotic Plaque Development with LDL Toxicity Effects. https://arxiv.org/abs/2304.02587

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