Atherosclerosis – the chronic build-up of fatty deposits in artery walls – is a leading cause of heart attacks and strokes. The process of atherosclerosis starts when low-density lipoprotein (LDL) cholesterol particles become trapped in the innermost layer of the artery wall, triggering an inflammatory response that attracts monocyte-derived macrophages (MDMs) to ingest the lipid. Over time, some MDMs become fat-laden “foam cells”, and their accumulation, together with extracellular lipids, can form lesions and plaques that narrow or stiffen the artery.
To better understand how the spatial distribution and lipid content of MDMs influence early lesion development, Ludwig Oxford’s Keith Chambers and Helen Byrne have developed a mathematical model based on images from human coronary arteries. The model, recently published in the Journal of Theoretical Biology, maps how lipids and macrophages build up and move within the vessel wall, revealing key interactions that shape plaque formation.
The model predicts that lipids initially accumulate deep in the artery wall due to non-uniform LDL retention. The model also finds that lipid-laden macrophages have shorter lifespans and reduced mobility, which influences where these cells gather and how plaques evolve. At steady state these effects can shift the composition of lesions, reducing the total lipid content and altering the depth of macrophage infiltration.
By linking cell behaviour to lipid content and spatial position, the study sheds light on fundamental processes in plaque growth and stability. This modelling framework could help identify new targets for therapies aimed at slowing or preventing atherosclerosis in its earliest stages.