A lipid-structured mathematical model of atherosclerosis with macrophage proliferation

TL;DR

This paper extends a mathematical model of atherosclerosis to include macrophage proliferation, revealing how proliferation influences plaque development and lipid distribution within macrophages, with implications for understanding plaque stability.

Contribution

It introduces a non-local proliferation term into a lipid-structured model, providing new insights into plaque composition and macrophage behavior in atherosclerosis.

Findings

Proliferation reduces necrotic core size.

Proliferation spreads lipid load among macrophages.

Proliferative and recruitment-dominant plaques differ mainly in lipid distribution.

Abstract

We extend the lipid-structured model for atherosclerotic plaque development of Ford et al. (2019) to account for macrophage proliferation. Proliferation is modelled as a non-local decrease in the lipid structural variable that is similar to the treatment of cell division in size-structured models (e.g. Efendiev et al. (2018)). Steady state analysis indicates that proliferation assists in reducing eventual necrotic core size and acts to spread the lipid load of the macrophage population amongst the cells. The relative contribution of plaque macrophages by proliferation and recruitment from the bloodstream is also examined. The model suggests that a more proliferative plaque differs from an equivalent (same lipid content and cell count) recruitment-dominant plaque only in the way lipid is distributed amongst the macrophages.