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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\u201363, 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 both the total quantity of lipid in the plaque and the distribution of lipid between the live cells, dead cells and necrotic core. The consequences of macrophage lipid-dependence are often unpredictable because lipid-dependent effects introduce subtle, nonlinear interactions between the modelled cell behaviours. These observations highlight the importance of mathematical modelling in unravelling the complexities of macrophage lipid accumulation during atherosclerotic plaque formation.<\/jats:p>","DOI":"10.1007\/s11538-023-01193-w","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T15:01:58Z","timestamp":1692111718000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Lipid-Structured Model of Atherosclerotic Plaque Macrophages with Lipid-Dependent Kinetics"],"prefix":"10.1007","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1938-0440","authenticated-orcid":false,"given":"Michael G.","family":"Watson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith L.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary R.","family":"Myerscough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"1193_CR1","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1007\/s10439-019-02268-3","volume":"47","author":"NA Avgerinos","year":"2019","unstructured":"Avgerinos NA, Neofytou P (2019) Mathematical modelling and simulation of atherosclerosis formation and progress: a review. 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