  Atherosclerotic plaques are fatty growths in artery walls that cause heart
attacks and strokes. Plaque formation is orchestrated by macrophages that are
recruited to the artery wall to consume and remove blood-derived lipids, such
as low-density lipoprotein (LDL). Ineffective lipid removal, due to macrophage
death and other factors, leads to the accumulation of lipid-loaded macrophages
and formation of a necrotic core. Experimental observations suggest that
macrophage functionality varies with the extent of lipid loading. However,
little is known about the resultant influence on plaque fate. Extending work by
Ford et al. (2019) and Chambers et al. (2022), we develop a plaque model in
which macrophages are classified by their ingested lipid content and behave in
a lipid-dependent manner. The model, a system of partial-integro differential
equations, considers several macrophage behaviours. These include: recruitment
to the artery wall; proliferation and apoptosis; ingestion of LDL, apoptotic
cells and necrotic lipid; emigration from the artery wall; and necrosis of
apoptotic cells. Here, we consider apoptosis, emigration and proliferation to
be lipid-dependent. We model lipid-dependence in these behaviours with
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. For
lipid-dependent apoptosis and lipid-dependent emigration simulations, we find
significant differences in outcomes for cases that ultimately converge on the
same net rate of apoptosis or emigration.
