A Lipid-Structured Model of Atherosclerotic Plaque Macrophages with Lipid-Dependent Kinetics

Bull Math Biol. 2023 Aug 15;85(9):85. doi: 10.1007/s11538-023-01193-w.ABSTRACTAtherosclerotic plaques are fatty growths in artery walls that cause heart attacks and strokes. Plaque formation is driven by macrophages that are recruited to the artery wall. These cells consume and remove blood-derived lipids, such as modified low-density lipoprotein. Ineffective lipid removal, due to macrophage death and other factors, leads to the accumulation of lipid-loaded macrophages and formation of a necrotic lipid core. Experimental observations suggest that macrophage functionality varies with the extent of lipid loading. However, little is known about the influence of macrophage lipid loads on plaque fate. Extending work by Ford et al. (J Theor Biol 479:48-63, 2019) and Chambers et al. (A lipid-structured model of atherosclerosis with macrophage proliferation, 2022), we develop a plaque model where macrophages are structured by their ingested lipid load and behave in a lipid-dependent manner. The model considers several macrophage behaviours, including recruitment to and emigration from the artery wall; proliferation and apotosis; ingestion of plaque lipids; and secondary necrosis of apoptotic cells. We consider apoptosis, emigration and proliferation to be lipid-dependent and we model these effects using experimentally informed functions of the internalised lipid load. Our results demonstrate that lipid-dependent macrophage behaviour can substantially alter plaque fate by changing bot...
Source: Bulletin of Mathematical Biology - Category: Bioinformatics Authors: Source Type: research