A lipid-structured model for macrophage populations in atherosclerotic plaques

Abstract

Atherosclerosis is a chronic inflammatory disease driven by the accumulation of pro-inflammatory, lipid-loaded macrophages at sites inside artery walls. These accumulations lead to the development of atherosclerotic plaques. The rupture of plaques that contain lipid-rich necrotic cores can trigger heart attacks and strokes via occlusion of blood vessels. We construct and analyse a system of partial integro-differential equations that model lipid accumulation by macrophages, the generation of apoptotic cells and the formation of the necrotic core. The model accounts for the following cell behaviours: monocyte recruitment into the plaque and differentiation into macrophages; macrophage ingestion of low density lipoproteins (LDL) and of apoptotic cells and necrotic material; lipid offloading to high density lipoproteins (HDL); macrophage emigration; and apoptosis of macrophages and necrosis of apoptotic cells. With this model, we study how changes in parameters predict the characteristic features of plaque pathology. In particular, we find the qualitative form of lipid distribution across the macrophage population and show that high lipid loads can occur in the absence of LDL ingestion. We also demonstrate the importance of macrophage emigration in mitigating and resolving inflammation and plaque lipid accumulation.

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

“…S2, I and J ). Lipid droplet formation in macrophages can be induced by the uptake of apoptotic cells ( Ward et al, 2018 ; Ford et al, 2019 ; D’Avila et al, 2011 ), suggesting PAMM1a function in the clearance of cellular debris and repair of the SCT following damage. If this is the case, PAMM1a might display transcriptomic similarities to macrophages in damaged, fibrotic tissues.…”

Macrophage Plasticity and Atherosclerosis Therapy

“…These foam macrophages express many lipid-processing genes and low levels of inflammatory genes compared to the non-foam macrophages (Kim et al, 2018). A mathematical model used for describing lipid accumulation in macrophages and the subsequent changes was established recently (Ford et al, 2019).…”

A prediction tool for plaque progression based on patient-specific multi-physical modeling

“…Besides the developments of novel imaging techniques, mathematical modeling and numerical simulation have been proven useful for quantitatively assessing the dynamic changes of cellular and acellular components involved in the plaque microenvironment and predicting plaque growth and possible rupture [14,15]. In our previous studies, we have developed a multi-physical mathematical model by coupling lipid deposition, inflammation, neovascularization and intraplaque hemorrhage, to investigate the pathophysiological responses of plaques to dynamic changes in the microenvironment [16,17].…”